Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hip...Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal neurogenesis.Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s disease.Recent evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy people.This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease.Therefore,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis.Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD mice.RNA sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein formation.In conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.展开更多
Repetitive transcranial magnetic stimulation(r TMS)has been shown to effectively improve impaired swallowing in Parkinson's disease(PD)patients with dysphagia.However,little is known about how r TMS affects the co...Repetitive transcranial magnetic stimulation(r TMS)has been shown to effectively improve impaired swallowing in Parkinson's disease(PD)patients with dysphagia.However,little is known about how r TMS affects the corresponding brain regions in this patient group.In this casecontrol study,we examined data from 38 PD patients with dysphagia who received treatment at Beijing Rehabilitation Medicine Academy,Capital Medical University.The patients received high-frequency r TMS of the motor cortex once per day for 10 successive days.Changes in brain activation were compared via functional magnetic resonance imaging in PD patients with dysphagia and healthy controls.The results revealed that before treatment,PD patients with dysphagia showed greater activation in the precentral gyrus,supplementary motor area,and cerebellum compared with healthy controls,and this enhanced activation was weakened after treatment.Furthermore,before treatment,PD patients with dysphagia exhibited decreased activation in the parahippocampal gyrus,caudate nucleus,and left thalamus compared with healthy controls,and this activation increased after treatment.In addition,PD patients with dysphagia reported improved subjective swallowing sensations after r TMS.These findings suggest that swallowing function in PD patients with dysphagia improved after r TMS of the motor cortex.This may have been due to enhanced activation of the caudate nucleus and parahippocampal gyrus.The study protocol was approved by the Ethics Committee of Beijing Rehabilitation Hospital of Capital Medical University(approval No.2018 bkky017)on March 6,2018 and was registered with Chinese Clinical Trial Registry(registration No.Chi CTR 1800017207)on July 18,2018.展开更多
Objective:To explore the characteristics of metabolic changes in patients with post-traumatic stress disorder through 1H-MRS in neuroanatomical circuit comparing with age-matches controls.Methods:Fifty patients with p...Objective:To explore the characteristics of metabolic changes in patients with post-traumatic stress disorder through 1H-MRS in neuroanatomical circuit comparing with age-matches controls.Methods:Fifty patients with post-traumatic stress disorder and SO gender-and agematched normal controls were involved.The neurochemical abnormalities including the levels of choline(Cho)/ creatine(Cr) and N-acetylaspartate(NAA)/Cr were measured respectively in hippocampus and the anterior cingulate gyrus with three-dimension 1H-proton specrroscopy(3D 1H-MRS).Results:The values of NAA/Cr ratios in hippocampus and the anterior cingulate gyrus were significant lower in patients with post-traumatic stress disorder(1.71±0.32,left l.58±0.29, right 1.55±0.31) than that in controls(2.24±0.41,left 1.98±0.27,right 2.02±0.36)(P【0.05).but the values of Cho/Cr in hippocampus(left 1.64±0.23,right 1.66±0.34) were no significant with that of controls(left 1.48±0.29,right 1.54±0.38).Values of Cho/Cr in cingulate gyrus were significant higher in post-traumatic stress disorder patients(I.88±0.44) than that in controls(1.37.±0.32) (P【0.05).Conclusions:The results indicate some special neurochemical and histological structure changes in post-traumatic stress disorder patients,which might occurre earlier in anterior cingulate gyrusthe than in hippocampus.展开更多
N-methyl-D-aspartate receptor hypofunction is the basis of pathophysiology in schizophrenia. Blocking the N-methyl-D-aspartate receptor impairs learning and memory abilities and induces pathological changes in the bra...N-methyl-D-aspartate receptor hypofunction is the basis of pathophysiology in schizophrenia. Blocking the N-methyl-D-aspartate receptor impairs learning and memory abilities and induces pathological changes in the brain. Previous studies have paid little attention to the role of the N-methyl-D-aspartate receptor subunit 1 (NR1) in neurogenesis in the hippocampus of schizophrenia. A mouse model of schizophrenia was established by intraperitoneal injection of 0.6 mg/kg MK-801, once a day, for 14 days. In N-methyl-D-aspartate-treated mice, N-methyl-D-aspartate was administered by intracerebroventricular injection in schizophrenia mice on day 15. The number of NR1-, Ki67- or BrdU-immunoreactive cells in the dentate gyrus was measured by immunofluorescence staining. Our data showed the number of NR1-immunoreactive cells increased along with the decreasing numbers of BrdU- and Ki67-immunoreactive cells in the schizophrenia groups compared with the control group. N-methyl-D-aspartate could reverse the above changes. These results indicated that NR1 can regulate neurogenesis in the hippocampal dentate gyrus of schizophrenia mice, supporting NR1 as a promising therapeutic target in the treatment of schizophrenia. This study was approved by the Experimental Animal Ethics Committee of the Ningxia Medical University, China (approval No. 2014-014) on March 6, 2014.展开更多
Stromal cell-derived factor-1 and its receptor CXCR4 are essential regulators of the neurogenesis that occurs in the adult hippocampal dentate gyrus.However,the effects of CXCR7,a new atypical receptor of stromal cell...Stromal cell-derived factor-1 and its receptor CXCR4 are essential regulators of the neurogenesis that occurs in the adult hippocampal dentate gyrus.However,the effects of CXCR7,a new atypical receptor of stromal cell-derived factor-1,on hippocampal neurogenesis after a stroke remain largely unknown.Our study is the first to investigate the effect of a CXCR7-neutralizing antibody on neurogenesis in the dentate gyrus and the associated recovery of cognitive function of rats in the chronic stage of cerebral ischemia.The rats were randomly divided into sham,sham+anti-CXCR7,ischemia and ischemia+anti-CXCR7 groups.Endothelin-1 was injected in the ipsilateral motor cortex and striatum to induce focal cerebral ischemia.Sham group rats were injected with saline instead of endothelin-1 via intracranial injection.Both sham and ischemic rats were treated with intraventricular infusions of CXCR7-neutralizing antibodies for 6 days 1 week after surgery.Immunofluorescence staining with doublecortin,a marker for neuronal precursors,was performed to assess the neurogenesis in the dentate gyrus.We found that anti-CXCR7 antibody infusion enhanced the proliferation and dendritic development of doublecortin-labeled cells in the dentate gyrus in both ischemic and sham-operated rats.Spatial learning and memory functions were assessed by Morris water maze tests 30-32 days after ischemia.CXCR7-neutralizing antibody treatment significantly reduced the escape latency of the spatial navigation trial and increased the time spent in the target quadrant of spatial probe trial in animals that received ischemic insult,but not in sham operated rats.These results suggest that CXCR7-neutralizing antibody enhances the neurogenesis in the dentate gyrus and improves the cognitive function after cerebral ischemia in rats.All animal experimental protocols and procedures were approved by the Institutional Animal Care and Use Committee of China Medical University(CMU16089 R)on December 8,2016.展开更多
The dentate gyrus subregion of the mammalian hippocampus is an adult neural stem cell niche and site of lifelong neurogenesis.Hypotheses regarding the role of adult-born neuron synaptic integration in hippocampal circ...The dentate gyrus subregion of the mammalian hippocampus is an adult neural stem cell niche and site of lifelong neurogenesis.Hypotheses regarding the role of adult-born neuron synaptic integration in hippocampal circuit function are framed by robust estimations of adultborn versus pre/perinatally-born neuron number.In contrast,the non-neurogenic functions of adult neural stem cells and their immediate progeny,such as secretion of bioactive growth factors and expression of extracellular matrix-modifying proteins,lack similar framing due to few estimates of their number versus other prominent secretory cells.Here,we apply immunohistochemical methods to estimate cell density of neural stem/progenitor cells versus other major classes of glial and endothelial cell types that are potentially secretory in the dentate gyrus of adult mice.Of the cell types quantified,we found that GFAP^(+)SOX2^(+)stellate astrocytes were the most numerous,followed by CD31^(+)endothelia,GFAP-SOX2^(+)intermediate progenitors,Olig2^(+)oligodendrocytes,Iba1+microglia,and GFAP^(+)SOX2^(+)radial glia-like neural stem cells.We did not observe any significant sex differences in density of any cell population.Notably,neural stem/progenitor cells were present at a similar density as several cell types known to have potent functional roles via their secretome.These findings may be useful for refining hypotheses regarding the contributions of these cell types to regulating hippocampal function and their potential therapeutic uses.All experimental protocols were approved by the Ohio State University Institutional Animal Care and Use Committee(protocol#2016A00000068)on July 14,2016.展开更多
Objective: To longitudinally assess dynamic changes of iron deposition and volume of the precentral gyrus and its correlation with clinical manifestations of Relapse-Remitting Multiple Sclerosis(RRMS) by using 3D enha...Objective: To longitudinally assess dynamic changes of iron deposition and volume of the precentral gyrus and its correlation with clinical manifestations of Relapse-Remitting Multiple Sclerosis(RRMS) by using 3D enhanced T2* weighted angiography(ESWAN). Methods: Thirty RRMS patients and thirty age- and sex-matched healthy controls were recruited and underwent ESWAN and 3D T1WI twice interval of one year with the same parameters. The mean phase values (MPVs) and volumes in precentral gyrus gray matter (PGM) were measured, and change of iron content and its correlation with volume, clinical manifestations were analyzed. Results: Compared with controls, the RRMS had higher iron deposition in both single-time measurements, but the volume decreased. Comparing to the first scan, we found significant difference in MPVs between the two times (P rs = 0.764, P rs = 0.592, P rs = 0.582, P rs = -0.399, P rs = -0.745, P rs = -0.367, P Conclusions: With the disease progression, the content of iron in PGM in RRMS patients is increasing, while the volume has no obvious change, suggesting that the iron deposition may precede or develop faster than cerebral atrophy.展开更多
BACKGROUND: Some studies suggest that the long-term potentiation (LTP) of synaptic transmission may be the basis for the neural synaptic plasticity of hippocampus, but can be evoked by various factors including electr...BACKGROUND: Some studies suggest that the long-term potentiation (LTP) of synaptic transmission may be the basis for the neural synaptic plasticity of hippocampus, but can be evoked by various factors including electroacupuncture. OBJECTIVE: To observe the effect of electroacupuncture on the activities of basic synaptic transmission in dentate gyrus of hippocampus and the changes of high frequency stimulation (HFS) induced activity of synaptic transmission in cerebral ischemic injured rats. DESIGN: A randomized control trial. SETTING: Shenzhen Hospital of Traditional Chinese Medicine affiliated to Guangzhou University of Traditional Chinese Medicine. MATERIALS: Sixty healthy male Wistar rats, weighing 150-250 g, were provided by the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. The experiment began after adaptation of environment for 1 week under standard experimental environment. The main experimental instruments included the programming electrical acupuncture apparatus (PCEA, product of the Institute of Acupuncture and Meridians, Anhui College of Traditional Chinese Medicine) and multichannel physiologic recorder (RM-86, Nihon Konden). METHODS: The experiment was carried out in Guangzhou University of Traditional Chinese Medicine between July 2003 and July 2004. ① Embedding of brain electrodes: In reference of the Pellegrino’s rat brain atlas, the bipolar electrode stimulator was embedded into the perforant path (PP) anterior to the entorhinal area with location coordinates of AP 7.5 mm, L 4.2 mm and H 3.0 mm, that is, 7.5 mm posterior to the anterior fontanelle, 4.2 mm laterally on the right side and 3.0 mm under the subcortex. The subcortex recorder electrode coordinates are AP 3.8 mm, L 2.5 mm and H 3.5 mm, located in the granular cell layer of the unilateral dentate gyrus (DG) of hippocampus, at the site of which an opening with the diameter of 1.5 mm was drilled for the purpose of embedding of the stimulating and recording electrodes, and at the site by mild adjusting the positions of these electrodes where maximal population spike (PS) was recorded, fastened the electrodes at last. ② The 60 rats were randomized into two major groups, namely, fundamental stimulation (FS) group (basic group) and high frequency stimulation (HFS) group. Each group was further divided into three subgroups respectively: Sham-operated subgroup (n=10): only exposed bilateral common carotid arteries without blocking their blood flow; Cerebral ischemia model subgroup (n=10): exposing bilateral common carotid arteries and blocking their blood flow; Ischemia plus electroacupuncture subgroup (n=10): blocked blood flow of bilateral common carotid arteries and received electroacupuncture. The electroacupuncture acupoints were the points of Du meridian, including Baihui (GV20), Dazhui (GV14), and points of Ren meridian, including Qihai (CV6) and Guanyuan (CV4). ③ Process of electroacupuncture: All the rats underwent testing stimulation (1/30 Hz frequency and 0.1 ms breadth) at 30 minutes before modeling, PS values were recorded as the indexes of the excitation of DG granular cell population, and the data were input to computer for data analysis. During the experiment, the intensity of stimulation was kept stable by adopting 1/2 the value of stimulation intensity that could induce maximal PS amplitude. In the basic group, PS were recorded for 120 minutes after modeling, and among the rats in the electroacupuncture group, PS was recorded at 10 minutes before and 60 minutes after blocking blood flow in the carotid artery during continuous electrical acupuncture. In the HFS group, HFS was given immediately after modeling, PS were recorded for 180 minutes at 10 minutes after HFS was given in the sham-operated group and model group, rats in the electroacupuncture group were treated with electroacupuncture for 60 minutes at 30 minutes after HFS was given, and PS was recorded for 180 minutes after 10 minutes. LTP was triggered by HFS and PS values were determined and recorded through measuring stimulations respectively 0, 10, 30, 60, 120 and 180 minutes after the evokes. ④ Methods for expressing the level of synaptic transmission: Each testing stimulus provoked one PS, and 10 successive amplitude values (V/mV) were averaged relevant to a certain time cut. The averaged PS of 6 time cuts at 30 minutes before modeling was made as basal synaptic transmission level as control. Synaptic transmission at each time cut was expressed as: p=(Vdifferent time cut/Vbasal)×100%. MAIN OUTCOME MEASURES: The differences of synaptic transmission level were compared among the subgroups in the basic group after models also among the subgroups in the HFS group after HFS. RESULTS: All the 60 rats were involved in the analysis of results. ① Comparison of synaptic transmission level at different time cut after modeling and the effect of electroacupuncture in the subgroups of the basic group: The synaptic transmission level in the sham-operated subgroup had no significant change within 120 minutes (P > 0.05). The synaptic transmission levels at 10, 30 and 60 minutes in the model subgroup were obviously lower than those in the sham-operated group [(60±7)%, (90±3)%, (93±4)%; (100±5)%, (102±6)%, (105±7)%, P < 0.05-0.01]. With the prolongation of time for ischemia/reperfusion, the synaptic transmission level gradually ascended to the normal level, and those at 90 and 120 minutes were close to those in the sham-operated group (P > 0.05). In the subgroup of electroacupuncture, the synaptic transmission levels at 10, 30, 60, 90 and 120 minutes were obviously higher than those in the model subgroup [(93±5)%, (106±10)%, (123±16)%, (145±20)%, (168±25)%; (96±7)%, (98±8)%, P < 0.05-0.01]. ② Comparison of synaptic transmission level at different time cut after HFS and the effect of electroacupuncture in the groups: In the sham-operated group, the synaptic transmission level after HFS increased significantly, and maintained without decrease within 180 minutes. In the model group, the synaptic transmission level at 0, 10, 30, 60, 120 and 180 minutes after HFS were obviously lower than those in the sham-operated group [(60±7)%, (95±9)%, (138±11)%, (141±13)%, (140±13)%, (138±15)%; (100±6)%, (182±21)%, (179 ±18)%, (177±18)%, (175±23)%, (178±24)%, P < 0.01]. The synaptic transmission level at 60, 120 and 180 minutes after HFS in the electroacupuncture group were close to those in the sham-operated group (P > 0.05), those at 120 and 180 minutes after HFS in the electroacupuncture group were obviously higher than those in the model group [(171±22)%, (181±25)%, P < 0.05-0.01]. CONCLUSION: Electroacupuncture could enhance the basic activity of synaptic transmission in the dentate gyrus of hippocampus in cerebral ischemic injury in rats. Electroacupuncture has obvious LTP effect on the activity of synaptic transmission induced by HFS.展开更多
BACKGROUND: Many researches have indicated that the imbalances of various amino acid transmitters and neurotransmitters in brain are involved in the formation of alcohol withdrawal, especially that glutamic acid is on...BACKGROUND: Many researches have indicated that the imbalances of various amino acid transmitters and neurotransmitters in brain are involved in the formation of alcohol withdrawal, especially that glutamic acid is one of the important transmitters for alcohol tolerance in central nervous system. OBJECTIVE: To observe the changes of excitatory amino acids in hippocampal dentate gyrus in rats with long-term alcohol drinking after withdrawal under consciousness, and investigate the therapeutic effect of topiramate on alcohol withdrawal. DESIGN: A randomized control animal experiment. SETTING: Department of Neurology, Affiliated Hospital of Yanbian University. MATERIALS: Thirty male Wistar rats of 4 months old, weighing 300-350 g, were purchased from the Experimental Animal Department, Medical College of Yanbian University. Topiramate was produced by Swish Cilag Company, and the batch number was 02CS063. METHODS: The experiments were carried out in the Department of Physiology, Medical College of Yanbian University from August 2005 to February 2006. ① The rats were divided randomly into three groups: control group (n=10), alcohol group (n=10) and topiramate-treated group (n=10). Rats in the alcohol group and topiramate-treated group were given intragastric perfusion of 500 g/L alcohol (10 mL/kg), once a day for 4 weeks successively, and then those in the topiramate-treated group were treated with 80 mg/kg topiramate at 24 hours after the last perfusion of alcohol, once a day for 3 days successively. Rats in the control group were intragastricly given isovolume saline. ② The withdrawal symptoms were assessed at 6, 30, 48 and 72 hours after the last perfusion of alcohol by using the withdrawal rating scale set by Erden et al, which had four observational indexes of stereotyped behaviors, agitation, tail stiffness and abnormal posture, each index was scored by 5 points, the higher the score, the more obvious the symptoms. ③ The contents of aspartic acid and glutamic acid in hippocampal dentate gyrus were detected with microdialysis technique and high-performance liquid chromatograpy (HPLC) respectively at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the three groups. MAIN OUTCOME MEASURES: ① Scoring results of alcohol withdrawal symptoms; ② Changes of the contents of aspartic acid and glutamic acid in hippocampal dentate gyrus at the alcohol withdrawal symptoms, and the effects of topiramate. RESULTS: Seven rats were excluded due to inaccurate localization and natural death, and 23 rats were involved in the analysis of results. ① In the alcohol group, the scores of alcohol withdrawal symptoms at 30 and 48 hours after the last perfusion of alcohol were obviously higher than those in the control group (10.50±0.96, 14.17±1.25; 3.50±0.92, 3.16±0.31; P < 0.01). In the topiramate-treated group, the scores at 30 hours after the last perfusion of alcohol (6.06±0.82, 3.50±0.92, P < 0.05), and the withdrawal scores at 48 and 72 hours were close to those in the control group (4.57±0.58, 3.30±0.71; 3.16±0.31, 3.66±0.67; P > 0.05). ② Changes of the contents of glutamic acid in hippocampal dentate gyrus: In the alcohol group, the content of glutamic acid at 48 hours after the last perfusion of alcohol was significantly increased as compared with that at 6 hours [(143.32±11.42)%, (99.12±0.69)%; P < 0.05], and that at 72 hours was close to that at 6 hours [(78.50±16.40)%, (99.12±0.69)%; P > 0.05]. The contents of glutamic acid had no obvious differences at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the topiramate-treated group [(100.30±0.37)%, (118.91±10.40)%, (99.55±12.81)%, (99.08±11.42)%; P > 0.05]. The content of glutamic acid at 48 hours after the last perfusion of alcohol in the topiramate-treated group was obviously lower than that in the alcohol group (P < 0.05), and those at 30 and 72 hours were close (P > 0.05). ③ Changes of the contents of aspartic acid in hippocampal dentate gyrus: In the alcohol group, the contents of aspartic acid at 30 and 48 hours after the last perfusion of alcohol were significantly increased as compared with that at 6 hours [(126.60±8.67)%, (129.17±10.40)%, (99.25±0.87)%; P < 0.05], and that at 72 hours was close to that at 6 hours [(89.87±9.93)%, (99.25±0.87)%; P > 0.05]. The contents of aspartic acid had no obvious differences at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the topiramate-treated group [(100.27±0.32)%, (120.81±12.63)%, (98.91±7.83)%, (85.92±8.07)%; P > 0.05]. The content of aspartic acid at 48 hours after the last perfusion of alcohol in the topiramate-treated group was obviously lower than that in the alcohol group (P < 0.05), and those at 30 and 72 hours were close (P > 0.05). CONCLUSION: ① The occurrences of alcohol withdrawal symptoms are correlated with the increased contents of excitatory amino acids in hippocampal dentate gyrus in rats. ② Topiramate can alleviate the alcohol withdrawal symptoms, which may be correlated with the decreased contents of excitatory amino acids in hippocampal dentate gyrus in rats.展开更多
<strong>Introduction:</strong> Numerous studies show the involvement of the cingulate gyrus in affective disorders, particularly in depression. With a preventive and curative aim, the authors raise questio...<strong>Introduction:</strong> Numerous studies show the involvement of the cingulate gyrus in affective disorders, particularly in depression. With a preventive and curative aim, the authors raise questions leading to therapeutic applications such as focal brain stimulation. The cingulate gyrus is the primary target of these brain stimulation therapies for the treatment of depression. The objective of this work is to establish anatomoclinical correlations and to deduce the therapeutic implications. <strong>Methodology:</strong> Our work is a review of the literature. The inventory of the cingulate gyrus and depression was based on the development of a critical synthesis of bibliographic knowledge. <strong>Results:</strong> We found a bipartite Brodmann subdivision which evolved into a subdivision into four regions of the cingulate gyrus. Descriptions of the cingulate gyrus boundaries are imprecise and divergent. The anterior end of the anterior cingulate cortex is a confirmed target of stimulation in the treatment of major and resistant depression, thus requiring the authors, a consensus in its delineation. Brodmann’s area 25 has been described as the main target of brain stimulation therapies. Dysfunction by local lesion or by alteration of the connectivity of Brodmann’s area has repercussions on these different structures to which it is interconnected. These disturbances when they are in the direction of collapse paint a picture similar to major depression. <strong>Conclusion: </strong>The anterior cingulate cortex is involved in depression. The functional system organization of affectivity will allow new brain stimulation techniques to act on the entire functional system or on one of its components.展开更多
Objective To investigate microsurgical techniques in bilateral falcine meningiomas of central gyrus region surgery. Methods Sixteen patients with bilateral falcine meningiomas in central gyrus region were treateded wi...Objective To investigate microsurgical techniques in bilateral falcine meningiomas of central gyrus region surgery. Methods Sixteen patients with bilateral falcine meningiomas in central gyrus region were treateded with a series of microsurgical techniques,including midline crossing craniotomy,dural cut in a strip fashion展开更多
Background:The involvement of specific basal ganglia-thalamocortical circuits in response inhibition has been extensively mapped in animal models.However,the pivotal nodes and directed causal regulation within this in...Background:The involvement of specific basal ganglia-thalamocortical circuits in response inhibition has been extensively mapped in animal models.However,the pivotal nodes and directed causal regulation within this inhibitory circuit in humans remains con-troversial.Objective:The main aim of the present study was to determine the causal information flow and critical nodes in the basal ganglia-thalamocortical inhibitory circuits and also to examine whether these are modulated by biological factors(i.e.sex)and behavioral performance.Methods:Here,we capitalize on the recent progress in robust and biologically plausible directed causal modeling(DCM-PEB)and a large response inhibition dataset(n=250)acquired with concomitant functional magnetic resonance imaging to determine key nodes,their causal regulation and modulation via biological variables(sex)and inhibitory performance in the inhibitory circuit encompassing the right inferior frontal gyrus(rIFG),caudate nucleus(rCau),globus pallidum(rGP),and thalamus(rThal).Results:The entire neural circuit exhibited high intrinsic connectivity and response inhibition critically increased causal projections from the rIFG to both rCau and rThal.Direct comparison further demonstrated that response inhibition induced an increasing rIFG inflow and increased the causal regulation of this region over the rCau and rThal.In addition,sex and performance influenced the functional architecture of the regulatory circuits such that women displayed increased rThal self-inhibition and decreased rThal to GP modulation,while better inhibitory performance was associated with stronger rThal to rIFG communication.Furthermore,control analyses did not reveal a similar key communication in a left lateralized model.Conclusions:Together,these findings indicate a pivotal role of the rIFG as input and causal regulator of subcortical response inhibition nodes.展开更多
Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However...Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.展开更多
Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system,particularly aberrant hippocampal neurogenesis.In this study,we applied in vivo fluorescent tracing using NestinCreERT2::Ro...Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system,particularly aberrant hippocampal neurogenesis.In this study,we applied in vivo fluorescent tracing using NestinCreERT2::Rosa26-tdTomato mice and analyzed the endogenous neurogenesis lineage progression of neural stem cells(NSCs)and dendritic spine formation of newborn neurons in the subgranular zone of the dentate gyrus.We found abnormal orientation of tamoxifen-induced tdTomato+(tdTom^(+))NSCs in adult mice 2 months after treatment with EtOH(5.0 g/kg,i.p.)for 7 consecutive days.EtOH markedly inhibited tdTom^(+)NSCs activation and hippocampal neurogenesis in mouse dentate gyrus from adolescence to adulthood.EtOH(100 mM)also significantly inhibited the proliferation to 39.2%and differentiation of primary NSCs in vitro.Adult mice exposed to EtOH also exhibited marked inhibitions in dendritic spine growth and newborn neuron maturation in the dentate gyrus,which was partially reversed by voluntary running or inhibition of the mammalian target of rapamycinenhancer of zeste homolog 2 pathway.In vivo tracing revealed that EtOH induced abnormal orientation of tdTom+NSCs and spatial misposition defects of newborn neurons,thus causing the disturbance of hippocampal neurogenesis and dendritic spine remodeling in mice.展开更多
Adult neurogenesis,the process of creating new neurons,involves the coordinated division,migration,and differentiation of neural stem cells.This process is restricted to neurogenic niches located in two distinct areas...Adult neurogenesis,the process of creating new neurons,involves the coordinated division,migration,and differentiation of neural stem cells.This process is restricted to neurogenic niches located in two distinct areas of the brain:the subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle,where new neurons are generated and then migrate to the olfactory bulb.Neurogenesis has been thought to occur only during the embryonic and early postnatal stages and to decline with age due to a continuous depletion of neural stem cells.Interestingly,recent years have seen tremendous progress in our understanding of adult brain neurogenesis,bridging the knowledge gap between embryonic and adult neurogenesis.Here,we discuss the current status of adult brain neurogenesis in light of what we know about neural stem cells.In this notion,we talk about the importance of intra cellular signaling molecules in mobilizing endogenous neural stem cell prolife ration.Based on the current understanding,we can declare that these molecules play a role in targeting neurogenesis in the mature brain.However,to achieve this goal,we need to avoid the undesired proliferation of neural stem cells by controlling the necessary checkpoints,which can lead to tumorigenesis and prove to be a curse instead of a blessing or hope.展开更多
It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous s...It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or renewed.Herein,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury.Central nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem cells.Because of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than neurons.Consequently,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function.Scientists have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming techniques.Used alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural circuit.Thus can integration re plenish lost neurons after central nervous system injury,by improving the local microenvironment.By regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons.This offers a novel approach for treating central nervous system injury.展开更多
MicroRNA-132(miR-132), a small RNA that regulates gene expression, is known to promote neurogenesis in the embryonic nervous system and adult brain.Although exposure to psychoactive substances can increase miR-132 exp...MicroRNA-132(miR-132), a small RNA that regulates gene expression, is known to promote neurogenesis in the embryonic nervous system and adult brain.Although exposure to psychoactive substances can increase miR-132 expression in cultured neural stem cells(NSCs)and the adult brain of rodents, little is known about its role in opioid addiction. So, we set out to determine the effect of miR-132 on differentiation of the NSCs and whether this effect is involved in opioid addiction using the rat morphine self-administration(MSA) model. We found that miR-132 overexpression enhanced the differentiation of NSCs in vivo and in vitro. Similarly, speci?c overexpression of miR-132 in NSCs of the adult hippocampal dentate gyrus(DG) during the acquisition stage of MSA potentiated morphine-seeking behavior. These ?ndings indicate that miR-132 is involved in opioid addiction,probably by promoting the differentiation of NSCs in the adult DG.展开更多
Prepulse inhibition(PPI) refers to a decreased response to a startling stimulus when another weaker stimulus precedes it. Most PPI studies have focused on the physiological startle reflex and fewer have reported the P...Prepulse inhibition(PPI) refers to a decreased response to a startling stimulus when another weaker stimulus precedes it. Most PPI studies have focused on the physiological startle reflex and fewer have reported the PPI of cortical responses. We recorded local field potentials(LFPs) in four monkeys and investigated whether the PPI of auditory cortical responses(alpha, beta, and gamma oscillations and evoked potentials) can be demonstrated in the caudolateral belt of the superior temporal gyrus(STGcb). We also investigated whether the presence of a conspecific, which draws attention away from the auditory stimuli, affects the PPI of auditory cortical responses. The PPI paradigm consisted of Pulse-only and Prepulse + Pulse trials that were presented randomly while the monkey was alone(ALONE) and while another monkey was present in the same room(ACCOMP). The LFPs to the Pulse were significantly suppressed by the Prepulse thus, demonstrating PPI of cortical responses in the STGcb. The PPI-related inhibition of the N1 amplitude of the evoked responses and cortical oscillations to the Pulse were not affected by the presence of a conspecific. In contrast, gamma oscillations and the amplitude of the N1 response to Pulse-only were suppressed in the ACCOMP condition compared to the ALONE condition. Thesefindings demonstrate PPI in the monkey STGcb and suggest that the PPI of auditory cortical responses in the monkey STGcb is a pre-attentive inhibitory process that is independent of attentional modulation.展开更多
基金supported by the National Natural Science Foundation of China,No.91849104(to YW)。
文摘Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal neurogenesis.Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s disease.Recent evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy people.This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease.Therefore,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis.Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD mice.RNA sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein formation.In conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.
基金supported by the Beijing Municipal Science and Technology Commission Capital Clinical Feature Applied Research Project of China,No.Z181100001718205(to WJG and PLH)。
文摘Repetitive transcranial magnetic stimulation(r TMS)has been shown to effectively improve impaired swallowing in Parkinson's disease(PD)patients with dysphagia.However,little is known about how r TMS affects the corresponding brain regions in this patient group.In this casecontrol study,we examined data from 38 PD patients with dysphagia who received treatment at Beijing Rehabilitation Medicine Academy,Capital Medical University.The patients received high-frequency r TMS of the motor cortex once per day for 10 successive days.Changes in brain activation were compared via functional magnetic resonance imaging in PD patients with dysphagia and healthy controls.The results revealed that before treatment,PD patients with dysphagia showed greater activation in the precentral gyrus,supplementary motor area,and cerebellum compared with healthy controls,and this enhanced activation was weakened after treatment.Furthermore,before treatment,PD patients with dysphagia exhibited decreased activation in the parahippocampal gyrus,caudate nucleus,and left thalamus compared with healthy controls,and this activation increased after treatment.In addition,PD patients with dysphagia reported improved subjective swallowing sensations after r TMS.These findings suggest that swallowing function in PD patients with dysphagia improved after r TMS of the motor cortex.This may have been due to enhanced activation of the caudate nucleus and parahippocampal gyrus.The study protocol was approved by the Ethics Committee of Beijing Rehabilitation Hospital of Capital Medical University(approval No.2018 bkky017)on March 6,2018 and was registered with Chinese Clinical Trial Registry(registration No.Chi CTR 1800017207)on July 18,2018.
基金funded by key Technology Projects in Hainan Province (Grant No.090209.zdxm2010043)
文摘Objective:To explore the characteristics of metabolic changes in patients with post-traumatic stress disorder through 1H-MRS in neuroanatomical circuit comparing with age-matches controls.Methods:Fifty patients with post-traumatic stress disorder and SO gender-and agematched normal controls were involved.The neurochemical abnormalities including the levels of choline(Cho)/ creatine(Cr) and N-acetylaspartate(NAA)/Cr were measured respectively in hippocampus and the anterior cingulate gyrus with three-dimension 1H-proton specrroscopy(3D 1H-MRS).Results:The values of NAA/Cr ratios in hippocampus and the anterior cingulate gyrus were significant lower in patients with post-traumatic stress disorder(1.71±0.32,left l.58±0.29, right 1.55±0.31) than that in controls(2.24±0.41,left 1.98±0.27,right 2.02±0.36)(P【0.05).but the values of Cho/Cr in hippocampus(left 1.64±0.23,right 1.66±0.34) were no significant with that of controls(left 1.48±0.29,right 1.54±0.38).Values of Cho/Cr in cingulate gyrus were significant higher in post-traumatic stress disorder patients(I.88±0.44) than that in controls(1.37.±0.32) (P【0.05).Conclusions:The results indicate some special neurochemical and histological structure changes in post-traumatic stress disorder patients,which might occurre earlier in anterior cingulate gyrusthe than in hippocampus.
基金supported by the National Natural Science Foundation of China,No.81160169(to JL),81460214(to JL),31660270(to JD),31460255(to JD)the Natural Science Foundation of Ningxia Hui Autonomous Region of China,No.2018AAC02005(to JL)
文摘N-methyl-D-aspartate receptor hypofunction is the basis of pathophysiology in schizophrenia. Blocking the N-methyl-D-aspartate receptor impairs learning and memory abilities and induces pathological changes in the brain. Previous studies have paid little attention to the role of the N-methyl-D-aspartate receptor subunit 1 (NR1) in neurogenesis in the hippocampus of schizophrenia. A mouse model of schizophrenia was established by intraperitoneal injection of 0.6 mg/kg MK-801, once a day, for 14 days. In N-methyl-D-aspartate-treated mice, N-methyl-D-aspartate was administered by intracerebroventricular injection in schizophrenia mice on day 15. The number of NR1-, Ki67- or BrdU-immunoreactive cells in the dentate gyrus was measured by immunofluorescence staining. Our data showed the number of NR1-immunoreactive cells increased along with the decreasing numbers of BrdU- and Ki67-immunoreactive cells in the schizophrenia groups compared with the control group. N-methyl-D-aspartate could reverse the above changes. These results indicated that NR1 can regulate neurogenesis in the hippocampal dentate gyrus of schizophrenia mice, supporting NR1 as a promising therapeutic target in the treatment of schizophrenia. This study was approved by the Experimental Animal Ethics Committee of the Ningxia Medical University, China (approval No. 2014-014) on March 6, 2014.
基金supported by the National Natural Science Foundation of China,No.81401002(to SSZ)
文摘Stromal cell-derived factor-1 and its receptor CXCR4 are essential regulators of the neurogenesis that occurs in the adult hippocampal dentate gyrus.However,the effects of CXCR7,a new atypical receptor of stromal cell-derived factor-1,on hippocampal neurogenesis after a stroke remain largely unknown.Our study is the first to investigate the effect of a CXCR7-neutralizing antibody on neurogenesis in the dentate gyrus and the associated recovery of cognitive function of rats in the chronic stage of cerebral ischemia.The rats were randomly divided into sham,sham+anti-CXCR7,ischemia and ischemia+anti-CXCR7 groups.Endothelin-1 was injected in the ipsilateral motor cortex and striatum to induce focal cerebral ischemia.Sham group rats were injected with saline instead of endothelin-1 via intracranial injection.Both sham and ischemic rats were treated with intraventricular infusions of CXCR7-neutralizing antibodies for 6 days 1 week after surgery.Immunofluorescence staining with doublecortin,a marker for neuronal precursors,was performed to assess the neurogenesis in the dentate gyrus.We found that anti-CXCR7 antibody infusion enhanced the proliferation and dendritic development of doublecortin-labeled cells in the dentate gyrus in both ischemic and sham-operated rats.Spatial learning and memory functions were assessed by Morris water maze tests 30-32 days after ischemia.CXCR7-neutralizing antibody treatment significantly reduced the escape latency of the spatial navigation trial and increased the time spent in the target quadrant of spatial probe trial in animals that received ischemic insult,but not in sham operated rats.These results suggest that CXCR7-neutralizing antibody enhances the neurogenesis in the dentate gyrus and improves the cognitive function after cerebral ischemia in rats.All animal experimental protocols and procedures were approved by the Institutional Animal Care and Use Committee of China Medical University(CMU16089 R)on December 8,2016.
基金a R00 Pathway to Independence Award from NIH/NINDS(R00NS089938to EDK).
文摘The dentate gyrus subregion of the mammalian hippocampus is an adult neural stem cell niche and site of lifelong neurogenesis.Hypotheses regarding the role of adult-born neuron synaptic integration in hippocampal circuit function are framed by robust estimations of adultborn versus pre/perinatally-born neuron number.In contrast,the non-neurogenic functions of adult neural stem cells and their immediate progeny,such as secretion of bioactive growth factors and expression of extracellular matrix-modifying proteins,lack similar framing due to few estimates of their number versus other prominent secretory cells.Here,we apply immunohistochemical methods to estimate cell density of neural stem/progenitor cells versus other major classes of glial and endothelial cell types that are potentially secretory in the dentate gyrus of adult mice.Of the cell types quantified,we found that GFAP^(+)SOX2^(+)stellate astrocytes were the most numerous,followed by CD31^(+)endothelia,GFAP-SOX2^(+)intermediate progenitors,Olig2^(+)oligodendrocytes,Iba1+microglia,and GFAP^(+)SOX2^(+)radial glia-like neural stem cells.We did not observe any significant sex differences in density of any cell population.Notably,neural stem/progenitor cells were present at a similar density as several cell types known to have potent functional roles via their secretome.These findings may be useful for refining hypotheses regarding the contributions of these cell types to regulating hippocampal function and their potential therapeutic uses.All experimental protocols were approved by the Ohio State University Institutional Animal Care and Use Committee(protocol#2016A00000068)on July 14,2016.
文摘Objective: To longitudinally assess dynamic changes of iron deposition and volume of the precentral gyrus and its correlation with clinical manifestations of Relapse-Remitting Multiple Sclerosis(RRMS) by using 3D enhanced T2* weighted angiography(ESWAN). Methods: Thirty RRMS patients and thirty age- and sex-matched healthy controls were recruited and underwent ESWAN and 3D T1WI twice interval of one year with the same parameters. The mean phase values (MPVs) and volumes in precentral gyrus gray matter (PGM) were measured, and change of iron content and its correlation with volume, clinical manifestations were analyzed. Results: Compared with controls, the RRMS had higher iron deposition in both single-time measurements, but the volume decreased. Comparing to the first scan, we found significant difference in MPVs between the two times (P rs = 0.764, P rs = 0.592, P rs = 0.582, P rs = -0.399, P rs = -0.745, P rs = -0.367, P Conclusions: With the disease progression, the content of iron in PGM in RRMS patients is increasing, while the volume has no obvious change, suggesting that the iron deposition may precede or develop faster than cerebral atrophy.
文摘BACKGROUND: Some studies suggest that the long-term potentiation (LTP) of synaptic transmission may be the basis for the neural synaptic plasticity of hippocampus, but can be evoked by various factors including electroacupuncture. OBJECTIVE: To observe the effect of electroacupuncture on the activities of basic synaptic transmission in dentate gyrus of hippocampus and the changes of high frequency stimulation (HFS) induced activity of synaptic transmission in cerebral ischemic injured rats. DESIGN: A randomized control trial. SETTING: Shenzhen Hospital of Traditional Chinese Medicine affiliated to Guangzhou University of Traditional Chinese Medicine. MATERIALS: Sixty healthy male Wistar rats, weighing 150-250 g, were provided by the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. The experiment began after adaptation of environment for 1 week under standard experimental environment. The main experimental instruments included the programming electrical acupuncture apparatus (PCEA, product of the Institute of Acupuncture and Meridians, Anhui College of Traditional Chinese Medicine) and multichannel physiologic recorder (RM-86, Nihon Konden). METHODS: The experiment was carried out in Guangzhou University of Traditional Chinese Medicine between July 2003 and July 2004. ① Embedding of brain electrodes: In reference of the Pellegrino’s rat brain atlas, the bipolar electrode stimulator was embedded into the perforant path (PP) anterior to the entorhinal area with location coordinates of AP 7.5 mm, L 4.2 mm and H 3.0 mm, that is, 7.5 mm posterior to the anterior fontanelle, 4.2 mm laterally on the right side and 3.0 mm under the subcortex. The subcortex recorder electrode coordinates are AP 3.8 mm, L 2.5 mm and H 3.5 mm, located in the granular cell layer of the unilateral dentate gyrus (DG) of hippocampus, at the site of which an opening with the diameter of 1.5 mm was drilled for the purpose of embedding of the stimulating and recording electrodes, and at the site by mild adjusting the positions of these electrodes where maximal population spike (PS) was recorded, fastened the electrodes at last. ② The 60 rats were randomized into two major groups, namely, fundamental stimulation (FS) group (basic group) and high frequency stimulation (HFS) group. Each group was further divided into three subgroups respectively: Sham-operated subgroup (n=10): only exposed bilateral common carotid arteries without blocking their blood flow; Cerebral ischemia model subgroup (n=10): exposing bilateral common carotid arteries and blocking their blood flow; Ischemia plus electroacupuncture subgroup (n=10): blocked blood flow of bilateral common carotid arteries and received electroacupuncture. The electroacupuncture acupoints were the points of Du meridian, including Baihui (GV20), Dazhui (GV14), and points of Ren meridian, including Qihai (CV6) and Guanyuan (CV4). ③ Process of electroacupuncture: All the rats underwent testing stimulation (1/30 Hz frequency and 0.1 ms breadth) at 30 minutes before modeling, PS values were recorded as the indexes of the excitation of DG granular cell population, and the data were input to computer for data analysis. During the experiment, the intensity of stimulation was kept stable by adopting 1/2 the value of stimulation intensity that could induce maximal PS amplitude. In the basic group, PS were recorded for 120 minutes after modeling, and among the rats in the electroacupuncture group, PS was recorded at 10 minutes before and 60 minutes after blocking blood flow in the carotid artery during continuous electrical acupuncture. In the HFS group, HFS was given immediately after modeling, PS were recorded for 180 minutes at 10 minutes after HFS was given in the sham-operated group and model group, rats in the electroacupuncture group were treated with electroacupuncture for 60 minutes at 30 minutes after HFS was given, and PS was recorded for 180 minutes after 10 minutes. LTP was triggered by HFS and PS values were determined and recorded through measuring stimulations respectively 0, 10, 30, 60, 120 and 180 minutes after the evokes. ④ Methods for expressing the level of synaptic transmission: Each testing stimulus provoked one PS, and 10 successive amplitude values (V/mV) were averaged relevant to a certain time cut. The averaged PS of 6 time cuts at 30 minutes before modeling was made as basal synaptic transmission level as control. Synaptic transmission at each time cut was expressed as: p=(Vdifferent time cut/Vbasal)×100%. MAIN OUTCOME MEASURES: The differences of synaptic transmission level were compared among the subgroups in the basic group after models also among the subgroups in the HFS group after HFS. RESULTS: All the 60 rats were involved in the analysis of results. ① Comparison of synaptic transmission level at different time cut after modeling and the effect of electroacupuncture in the subgroups of the basic group: The synaptic transmission level in the sham-operated subgroup had no significant change within 120 minutes (P > 0.05). The synaptic transmission levels at 10, 30 and 60 minutes in the model subgroup were obviously lower than those in the sham-operated group [(60±7)%, (90±3)%, (93±4)%; (100±5)%, (102±6)%, (105±7)%, P < 0.05-0.01]. With the prolongation of time for ischemia/reperfusion, the synaptic transmission level gradually ascended to the normal level, and those at 90 and 120 minutes were close to those in the sham-operated group (P > 0.05). In the subgroup of electroacupuncture, the synaptic transmission levels at 10, 30, 60, 90 and 120 minutes were obviously higher than those in the model subgroup [(93±5)%, (106±10)%, (123±16)%, (145±20)%, (168±25)%; (96±7)%, (98±8)%, P < 0.05-0.01]. ② Comparison of synaptic transmission level at different time cut after HFS and the effect of electroacupuncture in the groups: In the sham-operated group, the synaptic transmission level after HFS increased significantly, and maintained without decrease within 180 minutes. In the model group, the synaptic transmission level at 0, 10, 30, 60, 120 and 180 minutes after HFS were obviously lower than those in the sham-operated group [(60±7)%, (95±9)%, (138±11)%, (141±13)%, (140±13)%, (138±15)%; (100±6)%, (182±21)%, (179 ±18)%, (177±18)%, (175±23)%, (178±24)%, P < 0.01]. The synaptic transmission level at 60, 120 and 180 minutes after HFS in the electroacupuncture group were close to those in the sham-operated group (P > 0.05), those at 120 and 180 minutes after HFS in the electroacupuncture group were obviously higher than those in the model group [(171±22)%, (181±25)%, P < 0.05-0.01]. CONCLUSION: Electroacupuncture could enhance the basic activity of synaptic transmission in the dentate gyrus of hippocampus in cerebral ischemic injury in rats. Electroacupuncture has obvious LTP effect on the activity of synaptic transmission induced by HFS.
文摘BACKGROUND: Many researches have indicated that the imbalances of various amino acid transmitters and neurotransmitters in brain are involved in the formation of alcohol withdrawal, especially that glutamic acid is one of the important transmitters for alcohol tolerance in central nervous system. OBJECTIVE: To observe the changes of excitatory amino acids in hippocampal dentate gyrus in rats with long-term alcohol drinking after withdrawal under consciousness, and investigate the therapeutic effect of topiramate on alcohol withdrawal. DESIGN: A randomized control animal experiment. SETTING: Department of Neurology, Affiliated Hospital of Yanbian University. MATERIALS: Thirty male Wistar rats of 4 months old, weighing 300-350 g, were purchased from the Experimental Animal Department, Medical College of Yanbian University. Topiramate was produced by Swish Cilag Company, and the batch number was 02CS063. METHODS: The experiments were carried out in the Department of Physiology, Medical College of Yanbian University from August 2005 to February 2006. ① The rats were divided randomly into three groups: control group (n=10), alcohol group (n=10) and topiramate-treated group (n=10). Rats in the alcohol group and topiramate-treated group were given intragastric perfusion of 500 g/L alcohol (10 mL/kg), once a day for 4 weeks successively, and then those in the topiramate-treated group were treated with 80 mg/kg topiramate at 24 hours after the last perfusion of alcohol, once a day for 3 days successively. Rats in the control group were intragastricly given isovolume saline. ② The withdrawal symptoms were assessed at 6, 30, 48 and 72 hours after the last perfusion of alcohol by using the withdrawal rating scale set by Erden et al, which had four observational indexes of stereotyped behaviors, agitation, tail stiffness and abnormal posture, each index was scored by 5 points, the higher the score, the more obvious the symptoms. ③ The contents of aspartic acid and glutamic acid in hippocampal dentate gyrus were detected with microdialysis technique and high-performance liquid chromatograpy (HPLC) respectively at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the three groups. MAIN OUTCOME MEASURES: ① Scoring results of alcohol withdrawal symptoms; ② Changes of the contents of aspartic acid and glutamic acid in hippocampal dentate gyrus at the alcohol withdrawal symptoms, and the effects of topiramate. RESULTS: Seven rats were excluded due to inaccurate localization and natural death, and 23 rats were involved in the analysis of results. ① In the alcohol group, the scores of alcohol withdrawal symptoms at 30 and 48 hours after the last perfusion of alcohol were obviously higher than those in the control group (10.50±0.96, 14.17±1.25; 3.50±0.92, 3.16±0.31; P < 0.01). In the topiramate-treated group, the scores at 30 hours after the last perfusion of alcohol (6.06±0.82, 3.50±0.92, P < 0.05), and the withdrawal scores at 48 and 72 hours were close to those in the control group (4.57±0.58, 3.30±0.71; 3.16±0.31, 3.66±0.67; P > 0.05). ② Changes of the contents of glutamic acid in hippocampal dentate gyrus: In the alcohol group, the content of glutamic acid at 48 hours after the last perfusion of alcohol was significantly increased as compared with that at 6 hours [(143.32±11.42)%, (99.12±0.69)%; P < 0.05], and that at 72 hours was close to that at 6 hours [(78.50±16.40)%, (99.12±0.69)%; P > 0.05]. The contents of glutamic acid had no obvious differences at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the topiramate-treated group [(100.30±0.37)%, (118.91±10.40)%, (99.55±12.81)%, (99.08±11.42)%; P > 0.05]. The content of glutamic acid at 48 hours after the last perfusion of alcohol in the topiramate-treated group was obviously lower than that in the alcohol group (P < 0.05), and those at 30 and 72 hours were close (P > 0.05). ③ Changes of the contents of aspartic acid in hippocampal dentate gyrus: In the alcohol group, the contents of aspartic acid at 30 and 48 hours after the last perfusion of alcohol were significantly increased as compared with that at 6 hours [(126.60±8.67)%, (129.17±10.40)%, (99.25±0.87)%; P < 0.05], and that at 72 hours was close to that at 6 hours [(89.87±9.93)%, (99.25±0.87)%; P > 0.05]. The contents of aspartic acid had no obvious differences at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the topiramate-treated group [(100.27±0.32)%, (120.81±12.63)%, (98.91±7.83)%, (85.92±8.07)%; P > 0.05]. The content of aspartic acid at 48 hours after the last perfusion of alcohol in the topiramate-treated group was obviously lower than that in the alcohol group (P < 0.05), and those at 30 and 72 hours were close (P > 0.05). CONCLUSION: ① The occurrences of alcohol withdrawal symptoms are correlated with the increased contents of excitatory amino acids in hippocampal dentate gyrus in rats. ② Topiramate can alleviate the alcohol withdrawal symptoms, which may be correlated with the decreased contents of excitatory amino acids in hippocampal dentate gyrus in rats.
文摘<strong>Introduction:</strong> Numerous studies show the involvement of the cingulate gyrus in affective disorders, particularly in depression. With a preventive and curative aim, the authors raise questions leading to therapeutic applications such as focal brain stimulation. The cingulate gyrus is the primary target of these brain stimulation therapies for the treatment of depression. The objective of this work is to establish anatomoclinical correlations and to deduce the therapeutic implications. <strong>Methodology:</strong> Our work is a review of the literature. The inventory of the cingulate gyrus and depression was based on the development of a critical synthesis of bibliographic knowledge. <strong>Results:</strong> We found a bipartite Brodmann subdivision which evolved into a subdivision into four regions of the cingulate gyrus. Descriptions of the cingulate gyrus boundaries are imprecise and divergent. The anterior end of the anterior cingulate cortex is a confirmed target of stimulation in the treatment of major and resistant depression, thus requiring the authors, a consensus in its delineation. Brodmann’s area 25 has been described as the main target of brain stimulation therapies. Dysfunction by local lesion or by alteration of the connectivity of Brodmann’s area has repercussions on these different structures to which it is interconnected. These disturbances when they are in the direction of collapse paint a picture similar to major depression. <strong>Conclusion: </strong>The anterior cingulate cortex is involved in depression. The functional system organization of affectivity will allow new brain stimulation techniques to act on the entire functional system or on one of its components.
文摘Objective To investigate microsurgical techniques in bilateral falcine meningiomas of central gyrus region surgery. Methods Sixteen patients with bilateral falcine meningiomas in central gyrus region were treateded with a series of microsurgical techniques,including midline crossing craniotomy,dural cut in a strip fashion
基金supported by the by the National Key Research and Development Program of China (grant number:2018YFA0701400-BB)National Natural Science Foundation of China (grant numbers 31530032-KMK,91632117-BB,32200904 Qian Zhuang)Key Technological Projects of Guangdong Province (grant number 2018B030335001-KMK).
文摘Background:The involvement of specific basal ganglia-thalamocortical circuits in response inhibition has been extensively mapped in animal models.However,the pivotal nodes and directed causal regulation within this inhibitory circuit in humans remains con-troversial.Objective:The main aim of the present study was to determine the causal information flow and critical nodes in the basal ganglia-thalamocortical inhibitory circuits and also to examine whether these are modulated by biological factors(i.e.sex)and behavioral performance.Methods:Here,we capitalize on the recent progress in robust and biologically plausible directed causal modeling(DCM-PEB)and a large response inhibition dataset(n=250)acquired with concomitant functional magnetic resonance imaging to determine key nodes,their causal regulation and modulation via biological variables(sex)and inhibitory performance in the inhibitory circuit encompassing the right inferior frontal gyrus(rIFG),caudate nucleus(rCau),globus pallidum(rGP),and thalamus(rThal).Results:The entire neural circuit exhibited high intrinsic connectivity and response inhibition critically increased causal projections from the rIFG to both rCau and rThal.Direct comparison further demonstrated that response inhibition induced an increasing rIFG inflow and increased the causal regulation of this region over the rCau and rThal.In addition,sex and performance influenced the functional architecture of the regulatory circuits such that women displayed increased rThal self-inhibition and decreased rThal to GP modulation,while better inhibitory performance was associated with stronger rThal to rIFG communication.Furthermore,control analyses did not reveal a similar key communication in a left lateralized model.Conclusions:Together,these findings indicate a pivotal role of the rIFG as input and causal regulator of subcortical response inhibition nodes.
基金financially supported by the National Natural Science Foundation of China,No.81303115,81774042 (both to XC)the Pearl River S&T Nova Program of Guangzhou,No.201806010025 (to XC)+3 种基金the Specialty Program of Guangdong Province Hospital of Chinese Medicine of China,No.YN2018ZD07 (to XC)the Natural Science Foundatior of Guangdong Province of China,No.2023A1515012174 (to JL)the Science and Technology Program of Guangzhou of China,No.20210201 0268 (to XC),20210201 0339 (to JS)Guangdong Provincial Key Laboratory of Research on Emergency in TCM,Nos.2018-75,2019-140 (to JS)
文摘Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.
基金supported by the National Natural Science Foundation of China,Nos.31601175(to YL),81803508(to KZ),82074056(to JY)the Natural Science Foundation of Liaoning Province of China,No.20180550335(to YL)the Scientific Research Project of Educational Commission of Liaoning Province of China,No.201610163L22(to YL)。
文摘Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system,particularly aberrant hippocampal neurogenesis.In this study,we applied in vivo fluorescent tracing using NestinCreERT2::Rosa26-tdTomato mice and analyzed the endogenous neurogenesis lineage progression of neural stem cells(NSCs)and dendritic spine formation of newborn neurons in the subgranular zone of the dentate gyrus.We found abnormal orientation of tamoxifen-induced tdTomato+(tdTom^(+))NSCs in adult mice 2 months after treatment with EtOH(5.0 g/kg,i.p.)for 7 consecutive days.EtOH markedly inhibited tdTom^(+)NSCs activation and hippocampal neurogenesis in mouse dentate gyrus from adolescence to adulthood.EtOH(100 mM)also significantly inhibited the proliferation to 39.2%and differentiation of primary NSCs in vitro.Adult mice exposed to EtOH also exhibited marked inhibitions in dendritic spine growth and newborn neuron maturation in the dentate gyrus,which was partially reversed by voluntary running or inhibition of the mammalian target of rapamycinenhancer of zeste homolog 2 pathway.In vivo tracing revealed that EtOH induced abnormal orientation of tdTom+NSCs and spatial misposition defects of newborn neurons,thus causing the disturbance of hippocampal neurogenesis and dendritic spine remodeling in mice.
文摘Adult neurogenesis,the process of creating new neurons,involves the coordinated division,migration,and differentiation of neural stem cells.This process is restricted to neurogenic niches located in two distinct areas of the brain:the subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle,where new neurons are generated and then migrate to the olfactory bulb.Neurogenesis has been thought to occur only during the embryonic and early postnatal stages and to decline with age due to a continuous depletion of neural stem cells.Interestingly,recent years have seen tremendous progress in our understanding of adult brain neurogenesis,bridging the knowledge gap between embryonic and adult neurogenesis.Here,we discuss the current status of adult brain neurogenesis in light of what we know about neural stem cells.In this notion,we talk about the importance of intra cellular signaling molecules in mobilizing endogenous neural stem cell prolife ration.Based on the current understanding,we can declare that these molecules play a role in targeting neurogenesis in the mature brain.However,to achieve this goal,we need to avoid the undesired proliferation of neural stem cells by controlling the necessary checkpoints,which can lead to tumorigenesis and prove to be a curse instead of a blessing or hope.
基金supported by the National Natural Science Foundation of ChinaNos.82272171 (to ZY),82271403 (to XL),31971279 (to ZY),81941011 (to XL),31730030 (to XL)。
文摘It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or renewed.Herein,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury.Central nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem cells.Because of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than neurons.Consequently,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function.Scientists have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming techniques.Used alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural circuit.Thus can integration re plenish lost neurons after central nervous system injury,by improving the local microenvironment.By regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons.This offers a novel approach for treating central nervous system injury.
基金supported by grants from the National Natural Science Foundation(81471353 and 81771433)the National Basic Research Development Program of China(2015CB553500)the Science Fund for Creative Research Groups from the National Natural Science Foundation of China(81521063)
文摘MicroRNA-132(miR-132), a small RNA that regulates gene expression, is known to promote neurogenesis in the embryonic nervous system and adult brain.Although exposure to psychoactive substances can increase miR-132 expression in cultured neural stem cells(NSCs)and the adult brain of rodents, little is known about its role in opioid addiction. So, we set out to determine the effect of miR-132 on differentiation of the NSCs and whether this effect is involved in opioid addiction using the rat morphine self-administration(MSA) model. We found that miR-132 overexpression enhanced the differentiation of NSCs in vivo and in vitro. Similarly, speci?c overexpression of miR-132 in NSCs of the adult hippocampal dentate gyrus(DG) during the acquisition stage of MSA potentiated morphine-seeking behavior. These ?ndings indicate that miR-132 is involved in opioid addiction,probably by promoting the differentiation of NSCs in the adult DG.
基金supported by the aivo AALTO Project of Aalto Universitythe Academy of Finland(a grant No.P273147,a Project No.T31116,and the International Program/ChinaFinland 2014-2016)the National Natural Science Foundation of China(31271168)
文摘Prepulse inhibition(PPI) refers to a decreased response to a startling stimulus when another weaker stimulus precedes it. Most PPI studies have focused on the physiological startle reflex and fewer have reported the PPI of cortical responses. We recorded local field potentials(LFPs) in four monkeys and investigated whether the PPI of auditory cortical responses(alpha, beta, and gamma oscillations and evoked potentials) can be demonstrated in the caudolateral belt of the superior temporal gyrus(STGcb). We also investigated whether the presence of a conspecific, which draws attention away from the auditory stimuli, affects the PPI of auditory cortical responses. The PPI paradigm consisted of Pulse-only and Prepulse + Pulse trials that were presented randomly while the monkey was alone(ALONE) and while another monkey was present in the same room(ACCOMP). The LFPs to the Pulse were significantly suppressed by the Prepulse thus, demonstrating PPI of cortical responses in the STGcb. The PPI-related inhibition of the N1 amplitude of the evoked responses and cortical oscillations to the Pulse were not affected by the presence of a conspecific. In contrast, gamma oscillations and the amplitude of the N1 response to Pulse-only were suppressed in the ACCOMP condition compared to the ALONE condition. Thesefindings demonstrate PPI in the monkey STGcb and suggest that the PPI of auditory cortical responses in the monkey STGcb is a pre-attentive inhibitory process that is independent of attentional modulation.
