In a previous study,we found that long non-coding genes in Alzheimer’s disease(AD)are a result of endogenous gene disorders caused by the recruitment of microRNA(miRNA)and mRNA,and that miR-200a-3p and other represen...In a previous study,we found that long non-coding genes in Alzheimer’s disease(AD)are a result of endogenous gene disorders caused by the recruitment of microRNA(miRNA)and mRNA,and that miR-200a-3p and other representative miRNAs can mediate cognitive impairment and thus serve as new biomarkers for AD.In this study,we investigated the abnormal expression of miRNA and mRNA and the pathogenesis of AD at the epigenetic level.To this aim,we performed RNA sequencing and an integrative analysis of the cerebral cortex of the widely used amyloid precursor protein and presenilin-1 double transgenic mouse model of AD.Overall,129 mRNAs and 68 miRNAs were aberrantly expressed.Among these,eight down-regulated miRNAs and seven up-regulated miRNAs appeared as promising noninvasive biomarkers and therapeutic targets.The main enriched signaling pathways involved mitogen-activated kinase protein,phosphatidylinositol 3-kinase-protein kinase B,mechanistic target of rapamycin kinase,forkhead box O,and autophagy.An miRNA-mRNA network between dysregulated miRNAs and corresponding target genes connected with AD progression was also constructed.These miRNAs and mRNAs are potential biomarkers and therapeutic targets for new treatment strategies,early diagnosis,and prevention of AD.The present results provide a novel perspective on the role of miRNAs and mRNAs in AD.This study was approved by the Experimental Animal Care and Use Committee of Institute of Medicinal Biotechnology of Beijing,China(approval No.IMB-201909-D6)on September 6,2019.展开更多
Intracerebral hemorrhage(ICH)is a stroke subtype caused by spontaneous rupture of small vessels and bleeding into the brain parenchyma,resulting in cell death and sensorimotor deficits.Despite the greater prevalence o...Intracerebral hemorrhage(ICH)is a stroke subtype caused by spontaneous rupture of small vessels and bleeding into the brain parenchyma,resulting in cell death and sensorimotor deficits.Despite the greater prevalence of the ischemic form of stroke(87%),ICH has the highest mortality rate of all stroke subtypes.The striatum is the most affected structure in hemorrhagic stroke(35–70%),followed by cere-展开更多
BACKGROUND: Both c-Fos protein and nitricoxide synthase (NOS) have been used as general indexes in relative research about neurons, but it is lack of reports that c-Fos protein and NOS are applied synchronously to stu...BACKGROUND: Both c-Fos protein and nitricoxide synthase (NOS) have been used as general indexes in relative research about neurons, but it is lack of reports that c-Fos protein and NOS are applied synchronously to study the neurons of hypoxic fetal rats in uterus. OBJECTIVE: To study the effect of hypoxia in uterus on the expression of c-Fos protein and NOS in neurons of cerebral cortex from fetal rats and whether Angelica sinensis has the protective effect on these neurons in hypoxia. DESIGN: Randomized control experiment. SETTING: Department of Histology and Embryology, Luzhou Medical College. MATERIALS: Twelve adult female Wistar rats in oestrum and 1 male Wistar rat with bodymass from 220 to 250 g were chosen. Parenteral solution of Angelica sinensis mainly contained angelica sinensis, 10 mL/ampoule, was provided by Department of Agent of the Second Hospital Affiliated to Hubei Medical University (batch number: 01062310). METHODS: This experiment was completed in the Department of Histology and Embryology of Luzhou Medical College from September 2003 to June 2004. ① Twelve adult female Wistar rats in oestrum and 1 male Wistar rat were housed in one rearing cage. Vaginal embolus was performed on conceive female rat at 8:00 am next day. On the 15th conceiving day, all conceiving rats were divided randomly into three groups: control group, hypoxia group and Angelica group with 4 in each group. Rats in hypoxia group and Angelica group were modeled with hypotonic hypoxia in uterus. Angelica group: Rats were injected with 8 mL/kg Angelica sinensis injection through caudal veins before hypoxia. Hypoxia group: Rats were injected with the same volume of saline. Control group: Rats were not modeled and fed with normal way. ② Twenty embryos of rats were chosen randomly from each group and then routinely embedded in paraffin. Paraffin sections were cut from the brain of embryos to anterior fontanelle. Double-label staining was used to detect the expression of nNOS and c-Fos in neurons of cerebral cortex from embryos of rats. OLYMPUS Bx-50 microscope was used to observe sections and DP12 digit camera was also used under 400 times to detect types of cells. Under microscope, the number of c-Fos, NOS, c-Fos/NOS positive neurons in cerebral cortex from embryos of rats were counted in 2 fields with magnification of 400 in one section per animal. ③ The data in experiments were analyzed by one-way analysis of variance (ANOVA) followed by q test. MAIN OUTCOME MEASURES: ① Results of immunohistochemical double-label staining of c-Fos/NOS from cerebral cortex; ② Comparison of amount immunohistochemical double-label staining of c-Fos/NOS positive cells from cerebral cortex. RESULTS: ① The positive NOS cells and c-Fos/NOS cells in the three groups were mainly distributed in cerebral cortex, but positive c-Fos neurons were not observed. ② Positive NOS cells and c-Fos/NOS cells in hypoxia group were more than those in control group (76.55±12.02, 50.45±10.39; 33.35±7.42, 26.35 ±6.67, P < 0.05), but those in Angelica group were less than those in hypoxia group (51.70±9.82, 35.65 ±8.37, P < 0.05). CONCLUSION: Hypoxia can stimulate the increase of expression of c-Fos protein and NOS in neurons of cerebral cortex. However, Angelica sinensis can decrease this expression so as to play a protective role in cerebral neurons of hypoxic fetal rats.展开更多
BACKGROUND: Melatonin is a kind of hormones derived from pineal gland. Recent researches demonstrate that melatonin is characterized by anti-oxidation, anti-senility and destroying free radicals. While, effect and pat...BACKGROUND: Melatonin is a kind of hormones derived from pineal gland. Recent researches demonstrate that melatonin is characterized by anti-oxidation, anti-senility and destroying free radicals. While, effect and pathogenesis of pineal gland on learning ability should be further studied. OBJECTIVE: To investigate the effects of pinealectomy on learning abiliy, distribution of cholinesterase and expression of neuronal nitric oxide synthase (nNOS) in cerebral cortex of rats and probe into the effect of melatonin on learning ability, central cholinergic system and nNOS expression. DESIGN: Randomized grouping design and animal study. SETTING: Department of Neurology, the 187 Hospital of Chinese PLA. MATERIALS: A total of 12 male SD rats, of normal learning ability testing with Y-tape maze, of clean grade, weighing 190-210 g, aged 6 weeks, were selected in this study. METHODS: The experiment was carried out in the Department of Neurology, Zhujiang Hospital from July 1997 to June 2000. All SD rats were divided into experimental group (n =6, pinealectomy) and control group (n =6, sham operation). Seven days later, rats in both two groups were continuously fed for 33 days. ① Learning ability test: The learning ability of rats was tested by trisection Y-type maze and figured as attempting times. ② Expression of acetylcholinesterase (AchE) was detected by enzyme histochemistry and nNOS was measured by SABC method. ③ Quantitative analysis of AchE fibers: AchE fibers density in unit area (surface density) was surveyed with Leica Diaplan microscope and Leica Quantimet 500+ image analytic apparatus and quantitative parameter was set up for AchE fibers covering density (μm2) per 374 693.656 μm2, moreover, the AchE fibers density was measured in Ⅱ-Ⅳ layers of motor and somatosensory cortex (showing three layers per field of vision at one time), in radiative, lacunaria and molecular layers of CA1, CA2 and CA3 areas, and in lamina multiforms of dentate gyrus. Three tissue slices were picked up randomly in the same part of each rat, together six tissue slices for nNOS expression and four near view (× 400) were selected in the parts of right neocortex, medial septal nucleus-diagonal band nucleus (SM-DB), corpus striatus and hippocampus to count nNOS-positive cells. MAIN OUTCOME MEASURES: Learning ability; distribution and quantitative analysis of AchE fibers; expression of nNOS in various cerebral areas. RESULTS: The twelve rats were all involved in the final analysis. ① Learning ability test: The learning abilities before operation in the experimental group [(14.67±4.97) times] were consistent with those in the control group [(14.33±4.32) times, P > 0.05], the learning abilities in the experimental group at 40 days after pinealectomy [(28.67±2.42) times] were obviously more than those before pinealectomy and those in the control group after operation [(13.83±8.33) times, P < 0.01]. ② Results of AchE-positive fibers density in cerebral cortex of rats: The AChE-positive fibers densities in motor and somatosensory cortex, CA1, CA2 and CA3 areas of hippocampus and in lamina multiforms of dentate gyrus in the experimental group were obviously lower than those in the control group [experimental group: (15 244±1 339), (14 764±1 391), (12 991±970), (15 077±1 020), (19 546±1 489), (19 337±1 378) μm2; control group: (21 001±1 021), (17 930±2 225), (17 260±1 342), (18 911±1 048), (24 108±1 671), (22 917±1 909) μm2, P < 0.01]. ③ Expression of nNOS in various cerebral areas: nNOS-positive cells in cerebral cortex of rats of the experimental group were more, furthermore the ones in somatosensory cortex were slightly more in motor cortex and the number (5.90±0.68) was more than that in the control group (3.68±0.39,P < 0.05). The nNOS-positive cells in SM-DB (16.21±2.03) were markedly more than those in the control group (9.32±1.05,P < 0.01). The nNOS-positive cells in hippocampus (4.27±0.75) and in corpus striatus (9.35±2.58) were not different with those in the control group (3.94±0.53, 8.96±2.31, P > 0.05). CONCLUSION: Decrease of melatonin due to pinealectomy of rats can result in learning disorder, which may be related to trauma of cholinergic neuron in cerebral cortex which were caused by nitric oxide neurotoxicity arose from the overexpression of nNOS in cerebral neocortex and SM-DB.展开更多
The Brodmann area(BA)-based map is one of the most widely used cortical maps for studies of human brain functions and in clinical practice;however,the molecular architecture of BAs remains unknown.The present study pr...The Brodmann area(BA)-based map is one of the most widely used cortical maps for studies of human brain functions and in clinical practice;however,the molecular architecture of BAs remains unknown.The present study provided a global multiregional proteomic map of the human cerebral cortex by analyzing 29 BAs.These 29 BAs were grouped into 6 clusters based on similarities in proteomic patterns:the motor and sensory cluster,vision cluster,auditory and Broca’s area cluster,Wernicke’s area cluster,cingulate cortex cluster,and heterogeneous function cluster.We identified 474 cluster-specific and 134 BA-specific signature proteins whose functions are closely associated with specialized functions and disease vulnerability of the corresponding cluster or BA.The findings of the present study could provide explanations for the functional connections between the anterior cingulate cortex and sensorimotor cortex and for anxiety-related function in the sensorimotor cortex.The brain transcriptome and proteome comparison indicates that they both could reflect the function of cerebral cortex,but show different characteristics.These proteomic data are publicly available at the Human Brain Proteome Atlas(www.brain-omics.com).Our results may enhance our understanding of the molecular basis of brain functions and provide an important resource to support human brain research.展开更多
BACKGROUND: Immediate early gene (IEG) c-jun is a sensitive marker for functional status of nerve cells. Caspase-3 is a cysteine protease, which is a critical regulator of apoptosis. The effect of exogenous nerve grow...BACKGROUND: Immediate early gene (IEG) c-jun is a sensitive marker for functional status of nerve cells. Caspase-3 is a cysteine protease, which is a critical regulator of apoptosis. The effect of exogenous nerve growth factor (NGF) on the expression of c-jun mRNA and Caspase-3 protein in striate cortex of rats with transient global cerebral ischemia/reperfusion (IR) is unclear. OBJECTIVE: To study the protective effect of exogenous NGF on the brain of rats with transient global cerebral IR and its effecting pathway by observing the expression of c-jun mRNA and Caspase-3 protein. DESIGN: Randomized controlled animal trial. SETTING: Department of Neural Anatomy, Institute of Brain, China Medical University.MATERIALS:Eighteen healthy male SD rats of clean grade, aged 1 to 3 months, with body mass of 250 to 300 g, were involved in this study. NGF was provided by Dalian Svate Pharmaceutical Co.,Ltd. c-jun in situ hybridization detection kit, Caspase-3 antibody and SABC kit were purchased from Boster Biotechnology Co.,Ltd.METHODS: This trial was carried out in the Department of Neural Anatomy, Institute of Brain, China Medical University during September 2003 to April 2005. ① Experimental animals were randomized into three groups with 6 in each: sham-operation group, IR group and NGF group.②After the rats were anesthetized, the bilateral common carotid arteries and right external carotid arteries of rats were bluntly dissected and bilateral common carotid arteries were clamped for 30 minutes with bulldog clamps. Reperfusion began after buldog clamps were removed. Normal saline of 1mL and NGF (1×106 U/L) of 1 mL was injected into the common carotid artery of rats via right external carotid arteries in the IR group and NGF group respectively. The injection was conducted within 30 minutes, and then the right external carotid arteries were ligated. In the sham-operation group, occlusion of bilateral common carotid arteries and administration of drugs were omitted.③All the rats were executed by decollation at 3 hours after modeling. The animals were fixed with phosphate buffer solution (PBS, 0.1 mol/L) containing 40 g/L polyformaldehyde, their brains were quickly removed. The coronal section tissue mass containing striate cortex about 3 mm before line between two ears was taken and made into successive frozen sections.④The expression of c-jun mRNA and Caspase-3 protein in striate cortex of global cerebral ischemia rats were detected with in situ hybridization, immunohistochemistry and microscope image analysis. ⑤t test was used for comparing the difference of the measurement data.MAIN OUTCOME MEASURES:Comparison of the expression of IEG c-jun mRNA and Caspase-3 protein in striate cortex of brain of rats in each group.RESULTS:All the 18 SD rats were involved in the analysis of results. The c-jun mRNA and Caspase-3 protein positive reaction cells were found brown yellow in the striate cortex of rats, and most of them were in lamellas Ⅱ and Ⅲ, mainly presenting round or oval. The expression of c-jun mRNA and Caspase-3 protein in sham-operation group was weak or negative. The average gray value of c-jun mRNA and Caspase-3 protein in the IR group was significantly lower than that in the sham-operation group (49.52±4.13 vs. 95.48±5.28; 74.73±4.29 vs. 162.38±9.16,P < 0.01). The average gray value of c-jun mRNA and Caspase-3 protein in the NGF group was significantly higher than that in the IR group (63.96±4.25 vs.49.52±4.13; 83.98±4.13 vs. 74.73±4.29, P < 0.05). CONCLUSION: NGF can protect ischemic neurons by down-regulating the expression of c-jun mRNA and Caspase-3 protein in striate cortex of global cerebral ischemia rats.展开更多
Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the ex...Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons. However, there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function after cerebral infarction. We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function. This study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction. These patients were randomly assigned to three groups. The low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex(M1). The high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1. Finally, the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1. A total of 135 seconds of stimulation was applied in the sham group and high-frequency group. At 2 weeks after treatment, cortical latency of motor-evoked potentials and central motor conduction time were significantly lower compared with before treatment. Moreover, motor function scores were significantly improved. The above indices for the low- and high-frequency groups were significantly different compared with the sham group. However, there was no significant difference between the low- and high-frequency groups. The results show that low- and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction.展开更多
Objective:To investigate glucose metabolic alterations in cerebral cortical subareas using ^(18)F-labeled glucose derivative fluorodeoxyglucose(FDG)micro-positron emission tomography(PET)scanning in a rat renal ischem...Objective:To investigate glucose metabolic alterations in cerebral cortical subareas using ^(18)F-labeled glucose derivative fluorodeoxyglucose(FDG)micro-positron emission tomography(PET)scanning in a rat renal ischemia/reperfusion(RIR)model.Methods:Small-animal PET imaging in vivo was performed with ^(18)F-labeled FDG as a PET tracer to identify glucose metabolic alterations in cerebral cortical subregions using a rat model of RIR.Results:We found that the average standardized uptake value(SUV_(average))of the cerebral cortical subareas in the RIR group was significantly increased compared to the sham group(P<0.05).We also found that glucose uptake in different cortical subregions including the left auditory cortex,right medial prefrontal cortex,right para cortex,left retrosplenial cortex,right retrosplenial cortex,and right visual cortex was significantly increased in the RIR group(P<0.05),but there was no significant difference in the SUV_(avcrage) of right auditory cortex,left medial prefrontal cortex,left para cortex,and left visual cortex between the two groups.Conclusion:The ^(18)F-FDG PET data suggests that RIR causes a profound shift in the metabolic machinery of cerebral cortex subregions.展开更多
Aging is a global phenomenon and a complex biological process of all living beings that introduces various changes.During this physiological process,the brain is the most affected organ due to changes in its structura...Aging is a global phenomenon and a complex biological process of all living beings that introduces various changes.During this physiological process,the brain is the most affected organ due to changes in its structural and chemical functions,such as changes in plasticity and decrease in the number,diameter,length,and branching of dendrites and dendritic spines.Likewise,it presents a great reduction in volume resulting from the contraction of the gray matter.Consequently,aging can affect not only cognitive functions,including learning and memory,but also the quality of life of older people.As a result of the phenomena,various molecules with notable neuroprotective capacity have been proposed,which provide a therapeutic alternative for people under conditions of aging or some neurodegenerative diseases.It is important to indicate that in recent years the use of molecules with neurotrophic activity has shown interesting results when evaluated in in vivo models.This review aims to describe the neurotrophic potential of molecules such as resveratrol(3,5,4′-trihydroxystilbene),neurotrophins(brain-derived neurotrophic factor),and neurotrophic-type compounds such as the terminal carboxyl domain of the heavy chain of tetanus toxin,cerebrolysin,neuropeptide-12,and rapamycin.Most of these molecules have been evaluated by our research group.Studies suggest that these molecules exert an important therapeutic potential,restoring brain function in aging conditions or models of neurodegenerative diseases.Hence,our interest is in describing the current scientific evidence that supports the therapeutic potential of these molecules with active neurotrophic.展开更多
Neural stem/progenitor cell(NSC) transplantation has been shown to effectively improve neurological function in rats with hypoxic-ischemic brain damage.Vascular endothelial growth factor(VEGF) is a signaling protein t...Neural stem/progenitor cell(NSC) transplantation has been shown to effectively improve neurological function in rats with hypoxic-ischemic brain damage.Vascular endothelial growth factor(VEGF) is a signaling protein that stimulates angiogenesis and improves neural regeneration.We hypothesized that transplantation of VEGF-transfected NSCs would alleviate hypoxic-ischemic brain damage in neonatal rats.We produced and transfected a recombinant lentiviral vector containing the VEGF165 gene into cultured NSCs.The transfected NSCs were transplanted into the left sensorimotor cortex of rats 3 days after hypoxic-ischemic brain damage.Compared with the NSCs group,VEGF m RNA and protein expression levels were increased in the transgene NSCs group,and learning and memory abilities were significantly improved at 30 days.Furthermore,histopathological changes were alleviated in these animals.Our findings indicate that transplantation of VEGF-transfected NSCs may facilitate the recovery of neurological function,and that its therapeutic effectiveness is better than that of unmodified NSCs.展开更多
A review of recent animal models of Huntington’s disease showed many microRNAs had altered expression levels in the striatum and cerebral cortex,and which were mostly downregulated.Among the altered microRNAs were mi...A review of recent animal models of Huntington’s disease showed many microRNAs had altered expression levels in the striatum and cerebral cortex,and which were mostly downregulated.Among the altered microRNAs were miR-9/9*,miR-29b,miR-124a,miR-132,miR-128,miR-139,miR-122,miR-138,miR-23b,miR-135b,miR-181(all downregulated)and miR-448(upregulated),and similar changes had been previously found in Huntington’s disease patients.In the animal cell studies,the altered microRNAs included miR-9,miR-9*,miR-135b,miR-222(all downregulated)and miR-214(upregulated).In the animal models,overexpression of miR-155 and miR-196a caused a decrease in mutant huntingtin mRNA and protein level,lowered the mutant huntingtin aggregates in striatum and cortex,and improved performance in behavioral tests.Improved performance in behavioral tests also occurred with overexpression of miR-132 and miR-124.In the animal cell models,overexpression of miR-22 increased the viability of rat primary cortical and striatal neurons infected with mutant huntingtin and decreased huntingtin-enriched foci of≥2μm.Also,overexpression of miR-22 enhanced the survival of rat primary striatal neurons treated with 3-nitropropionic acid.Exogenous expression of miR-214,miR-146a,miR-150,and miR-125b decreased endogenous expression of huntingtin mRNA and protein in HdhQ111/HdhQ111 cells.Further studies with animal models of Huntington’s disease are warranted to validate these findings and identify specific microRNAs whose overexpression inhibits the production of mutant huntingtin protein and other harmful processes and may provide a more effective means of treating Huntington’s disease in patients and slowing its progression.展开更多
Platelet-derived growth factor receptor alpha(PDGFRα) is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whether...Platelet-derived growth factor receptor alpha(PDGFRα) is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whether there are differences in the distribution and morphology of oligodendrocyte precursor cells labeled by NG2 or PDGFRα in the developing neonatal rat brain remains unclear. In this study, by immunohistochemical staining, NG2 positive(NG2^+) cells were ubiquitous in the molecular layer, external pyramidal layer, internal pyramidal layer, and polymorphic layer of the cerebral cortex, and corpus callosum, external capsule, piriform cortex, and medial septal nucleus. NG2^+ cells were stellate or fusiform in shape with long processes that were progressively decreased and shortened over the course of brain development. The distribution and morphology of PDGFRα positive(PDGFRα^+) cells were coincident with NG2^+ cells. The colocalization of NG2 and PDGFRα in the cell bodies and processes of some cells was confirmed by double immunofluorescence labeling. Moreover, cells double-labeled for NG2 and PDGFRα were predominantly in the early postnatal stage of development. The numbers of NG2^+/PDGFRα^+ cells and PDGFRα^+ cells decreased, but the number of NG2^+ cells increased from postnatal days 3 to 14 in the developing brain. In addition, amoeboid microglial cells of the corpus callosum, newborn brain macrophages in the normal developing brain, did not express NG2 or PDGFRα, but NG2 expression was detected in amoeboid microglia after hypoxia. The present results suggest that NG2 and PDGFRα are specific markers of oligodendrocyte precursor cells at different stages during early development. Additionally, the NG2 protein is involved in inflammatory and pathological processes of amoeboid microglial cells.展开更多
The neonatal hypoxic-ischemic encephalopathy(HIE)is an important cause of neurological morbidity and mortality in neonates.Cell therapy is considered a promising method for treating severe neurological disorders such ...The neonatal hypoxic-ischemic encephalopathy(HIE)is an important cause of neurological morbidity and mortality in neonates.Cell therapy is considered a promising method for treating severe neurological disorders such as this one.Stem cells have the capacity for self-renewal and differentiation into certain cell lineages.The present study was aimed to find out the most beneficial route of bone marrow-derived mesenchymal stem cells(BMSCs)administration for the attenuation of experimentally induced HIE in neonatal rats.Sixty neonatal rats were divided randomly into four groups.Group 1:control group.Group 2:rats were exposed to bilateral ligation of cephalic arteries.Group 3:rats were exposed to bilateral ligation of cephalic arteries and then underwent intravenous(IV)BMSC injection.Group 4:rats were exposed to bilateral ligation of cephalic arteries and then underwent intracerebroventricular(ICV)BMSC injection.The animals were evaluated by(a)neurobehavioral tests;(b)histopathology,i.e.,histological and immuno-histochemical studies;and(3)gene expression studies.The BMSC treated groups(3 and 4)showed improvement in neurobehavioral tests,histopathological studies,and gene expression,as compared to non-injected lesioned rats(Group 2)with better improvement in Group 4(ICV injections)than in Group 3(IV injections).展开更多
Visual information about an object is widely distributed over the cortex. The problem of how this information gets reassembled in consciousness is the “binding problem”. It is assumed in this paper that consciousnes...Visual information about an object is widely distributed over the cortex. The problem of how this information gets reassembled in consciousness is the “binding problem”. It is assumed in this paper that consciousness reads the distributed information as a laser reads a barcode;and that this solves the binding problem without resorting to oscillations, or synchronous signals, or any other form of mechanical association. Cortical distributions are made intelligible by consciousness that learns from childhood to recognize cortical arrays of single objects and project them onto the external world. An example shows how consciousness exercises its influence in the case of a well-known line drawing. When an object is constructed by consciousness there is no guarantee that the resulting image will be anything like the original object of observation. However, there is reason to believe that most of the visual images of our surroundings reflect real properties of those surroundings. These images have a constancy about them that is not always conveyed by the sensory input, but consistency in the external world can be learned by consciousness that is able to override the incongruities of the senses.展开更多
The aim of this study was to investigate the role of endogenous enkephalin in the cerebral antihyperalgesic action of gabapentin.Neuropathic pain models and antihyperalgesic effect of gabapentin were confirmed by the ...The aim of this study was to investigate the role of endogenous enkephalin in the cerebral antihyperalgesic action of gabapentin.Neuropathic pain models and antihyperalgesic effect of gabapentin were confirmed by the presentation and changes of mechanical allodynia and thermal hyperalgesia of operated mouse hind paws.The results suggested that endogenous enkephalin may not be involved in the antihyperalgesic effect of gabapentin.展开更多
Derived from neural stem cells(NSCs)and progenitor cells originated from the neuroectoderm,the nervous system presents an unprecedented degree of cellular diversity,interwoven to ensure correct connections for propaga...Derived from neural stem cells(NSCs)and progenitor cells originated from the neuroectoderm,the nervous system presents an unprecedented degree of cellular diversity,interwoven to ensure correct connections for propagating information and responding to environ-mental cues.NSCs and progenitor cells must integrate cell-intrinsic programs and environmental cues to achieve production of appropriate types of neurons and glia at appropriate times and places during develop-ment.These developmental dynamics are reflected in changes in gene expression,which is regulated by transcription factors and at the epigenetic level.From early commitment of neural lineage to functional plas-ticity in terminal differentiated neurons,epigenetic regulation is involved in every step of neural develop-ment.Here we focus on the recent advance in our un-derstanding of epigenetic regulation on orderly genera-tion of diverse neural cell types in the mammalian nervous system,an important aspect of neural devel-opment and regenerative medicine.展开更多
Human cortical radial glial cells are primary neural stem cells that give rise to cortical glutaminergic projection pyramidal neurons, glial cells (oligodendrocytes and astrocytes) and olfactory bulb GABAergic interne...Human cortical radial glial cells are primary neural stem cells that give rise to cortical glutaminergic projection pyramidal neurons, glial cells (oligodendrocytes and astrocytes) and olfactory bulb GABAergic interneurons. One of prominent features of the human cortex is enriched with glial cells, but there are major gaps in understanding how these glial cells are generated. Herein, by integrating analysis of published human cortical single-cell RNA-Seq datasets with our immunohistochemistical analyses, we show that around gestational week 18, EGFR-expressing human cortical truncated radial glial cells (tRGs) give rise to basal multipotent intermediate progenitors (bMIPCs) that express EGFR, ASCL1, OLIG2 and OLIG1. These bMIPCs undergo several rounds of mitosis and generate cortical oligodendrocytes, astrocytes and olfactory bulb interneurons. We also characterized molecular features of the cortical tRG. Integration of our findings suggests a general picture of the lineage progression of cortical radial glial cells, a fundamental process of the developing human cerebral cortex.展开更多
Mouse cortical radial glial cells(RGCs)are primary neural stem cells that give rise to cortical oligodendrocytes,astrocytes,and olfactory bulb(OB)GABAergic interneurons in late embryogenesis.There are fundamental gaps...Mouse cortical radial glial cells(RGCs)are primary neural stem cells that give rise to cortical oligodendrocytes,astrocytes,and olfactory bulb(OB)GABAergic interneurons in late embryogenesis.There are fundamental gaps in understanding how these diverse cell subtypes are generated.Here,by combining single-cell RNA-Seq with intersectional lineage analyses,we show that beginning at around E16.5,neocortical RGCs start to generate ASCL1^(+)EGFR^(+)apical multipotent intermediate progenitors(MIPCs),which then differentiate into basal MIPCs that express ASCL1,EGFR,OLIG2,and MKI67.These basal MIPCs undergo several rounds of divisions to generate most of the cortical oligodendrocytes and astrocytes and a subpopulation of OB interneurons.Finally,single-cell ATAC-Seq supported our model for the genetic logic underlying the specification and differentiation of cortical glial cells and OB interneurons.Taken together,this work reveals the process of cortical radial glial cell lineage progression and the developmental origins of cortical astrocytes and oligodendrocytes.展开更多
Research on the mechanical properties of brain tissue has received extensive attention.However,most of the current studies have been conducted at the phenomenological level.In this study,the indentation method was use...Research on the mechanical properties of brain tissue has received extensive attention.However,most of the current studies have been conducted at the phenomenological level.In this study,the indentation method was used to explore the difference in local mechanical properties among different regions of the porcine cerebral cortex.Further,hematoxylin-eosin and immunofluorescence staining methods were used to determine the correlation between the cellular density at different test points and mechanical properties of the porcine cerebral cortex.The frontal lobe exhibited the strongest viscosity.The temporal lobe displayed the lowest sensitivity to changes in the indentation speed,and the occipital lobe exhibited the highest shear modulus.Additionally,the shear modulus of different areas of the cerebral cortex was negatively correlated with the total number of local cells per unit area and positively correlated with the number of neuronal cell bodies per unit area.Exploration of the mechanical properties of the local brain tissue can provide basic data for the establishment of a finite element model of the brain and mechanical referential information for the implantation position of brain chips.展开更多
基金This study was supported by the National Natural Science Foundation of China(General Program),No.81673411the United Fund Project of National Natural Science Foundation of China,No.U1803281+1 种基金Young Medical Talents Award Project of Chinese Academy of Medical Sciences,No.2018RC350013Chinese Academy of Medical Sciences Innovation Project for Medical Science,No.2017-I2M-1-016(all to RL).
文摘In a previous study,we found that long non-coding genes in Alzheimer’s disease(AD)are a result of endogenous gene disorders caused by the recruitment of microRNA(miRNA)and mRNA,and that miR-200a-3p and other representative miRNAs can mediate cognitive impairment and thus serve as new biomarkers for AD.In this study,we investigated the abnormal expression of miRNA and mRNA and the pathogenesis of AD at the epigenetic level.To this aim,we performed RNA sequencing and an integrative analysis of the cerebral cortex of the widely used amyloid precursor protein and presenilin-1 double transgenic mouse model of AD.Overall,129 mRNAs and 68 miRNAs were aberrantly expressed.Among these,eight down-regulated miRNAs and seven up-regulated miRNAs appeared as promising noninvasive biomarkers and therapeutic targets.The main enriched signaling pathways involved mitogen-activated kinase protein,phosphatidylinositol 3-kinase-protein kinase B,mechanistic target of rapamycin kinase,forkhead box O,and autophagy.An miRNA-mRNA network between dysregulated miRNAs and corresponding target genes connected with AD progression was also constructed.These miRNAs and mRNAs are potential biomarkers and therapeutic targets for new treatment strategies,early diagnosis,and prevention of AD.The present results provide a novel perspective on the role of miRNAs and mRNAs in AD.This study was approved by the Experimental Animal Care and Use Committee of Institute of Medicinal Biotechnology of Beijing,China(approval No.IMB-201909-D6)on September 6,2019.
文摘Intracerebral hemorrhage(ICH)is a stroke subtype caused by spontaneous rupture of small vessels and bleeding into the brain parenchyma,resulting in cell death and sensorimotor deficits.Despite the greater prevalence of the ischemic form of stroke(87%),ICH has the highest mortality rate of all stroke subtypes.The striatum is the most affected structure in hemorrhagic stroke(35–70%),followed by cere-
基金the Natural Science Foundation of Sichuan Educational Bureau, No. Chuanjiaoji (2001) 149-01LA40
文摘BACKGROUND: Both c-Fos protein and nitricoxide synthase (NOS) have been used as general indexes in relative research about neurons, but it is lack of reports that c-Fos protein and NOS are applied synchronously to study the neurons of hypoxic fetal rats in uterus. OBJECTIVE: To study the effect of hypoxia in uterus on the expression of c-Fos protein and NOS in neurons of cerebral cortex from fetal rats and whether Angelica sinensis has the protective effect on these neurons in hypoxia. DESIGN: Randomized control experiment. SETTING: Department of Histology and Embryology, Luzhou Medical College. MATERIALS: Twelve adult female Wistar rats in oestrum and 1 male Wistar rat with bodymass from 220 to 250 g were chosen. Parenteral solution of Angelica sinensis mainly contained angelica sinensis, 10 mL/ampoule, was provided by Department of Agent of the Second Hospital Affiliated to Hubei Medical University (batch number: 01062310). METHODS: This experiment was completed in the Department of Histology and Embryology of Luzhou Medical College from September 2003 to June 2004. ① Twelve adult female Wistar rats in oestrum and 1 male Wistar rat were housed in one rearing cage. Vaginal embolus was performed on conceive female rat at 8:00 am next day. On the 15th conceiving day, all conceiving rats were divided randomly into three groups: control group, hypoxia group and Angelica group with 4 in each group. Rats in hypoxia group and Angelica group were modeled with hypotonic hypoxia in uterus. Angelica group: Rats were injected with 8 mL/kg Angelica sinensis injection through caudal veins before hypoxia. Hypoxia group: Rats were injected with the same volume of saline. Control group: Rats were not modeled and fed with normal way. ② Twenty embryos of rats were chosen randomly from each group and then routinely embedded in paraffin. Paraffin sections were cut from the brain of embryos to anterior fontanelle. Double-label staining was used to detect the expression of nNOS and c-Fos in neurons of cerebral cortex from embryos of rats. OLYMPUS Bx-50 microscope was used to observe sections and DP12 digit camera was also used under 400 times to detect types of cells. Under microscope, the number of c-Fos, NOS, c-Fos/NOS positive neurons in cerebral cortex from embryos of rats were counted in 2 fields with magnification of 400 in one section per animal. ③ The data in experiments were analyzed by one-way analysis of variance (ANOVA) followed by q test. MAIN OUTCOME MEASURES: ① Results of immunohistochemical double-label staining of c-Fos/NOS from cerebral cortex; ② Comparison of amount immunohistochemical double-label staining of c-Fos/NOS positive cells from cerebral cortex. RESULTS: ① The positive NOS cells and c-Fos/NOS cells in the three groups were mainly distributed in cerebral cortex, but positive c-Fos neurons were not observed. ② Positive NOS cells and c-Fos/NOS cells in hypoxia group were more than those in control group (76.55±12.02, 50.45±10.39; 33.35±7.42, 26.35 ±6.67, P < 0.05), but those in Angelica group were less than those in hypoxia group (51.70±9.82, 35.65 ±8.37, P < 0.05). CONCLUSION: Hypoxia can stimulate the increase of expression of c-Fos protein and NOS in neurons of cerebral cortex. However, Angelica sinensis can decrease this expression so as to play a protective role in cerebral neurons of hypoxic fetal rats.
文摘BACKGROUND: Melatonin is a kind of hormones derived from pineal gland. Recent researches demonstrate that melatonin is characterized by anti-oxidation, anti-senility and destroying free radicals. While, effect and pathogenesis of pineal gland on learning ability should be further studied. OBJECTIVE: To investigate the effects of pinealectomy on learning abiliy, distribution of cholinesterase and expression of neuronal nitric oxide synthase (nNOS) in cerebral cortex of rats and probe into the effect of melatonin on learning ability, central cholinergic system and nNOS expression. DESIGN: Randomized grouping design and animal study. SETTING: Department of Neurology, the 187 Hospital of Chinese PLA. MATERIALS: A total of 12 male SD rats, of normal learning ability testing with Y-tape maze, of clean grade, weighing 190-210 g, aged 6 weeks, were selected in this study. METHODS: The experiment was carried out in the Department of Neurology, Zhujiang Hospital from July 1997 to June 2000. All SD rats were divided into experimental group (n =6, pinealectomy) and control group (n =6, sham operation). Seven days later, rats in both two groups were continuously fed for 33 days. ① Learning ability test: The learning ability of rats was tested by trisection Y-type maze and figured as attempting times. ② Expression of acetylcholinesterase (AchE) was detected by enzyme histochemistry and nNOS was measured by SABC method. ③ Quantitative analysis of AchE fibers: AchE fibers density in unit area (surface density) was surveyed with Leica Diaplan microscope and Leica Quantimet 500+ image analytic apparatus and quantitative parameter was set up for AchE fibers covering density (μm2) per 374 693.656 μm2, moreover, the AchE fibers density was measured in Ⅱ-Ⅳ layers of motor and somatosensory cortex (showing three layers per field of vision at one time), in radiative, lacunaria and molecular layers of CA1, CA2 and CA3 areas, and in lamina multiforms of dentate gyrus. Three tissue slices were picked up randomly in the same part of each rat, together six tissue slices for nNOS expression and four near view (× 400) were selected in the parts of right neocortex, medial septal nucleus-diagonal band nucleus (SM-DB), corpus striatus and hippocampus to count nNOS-positive cells. MAIN OUTCOME MEASURES: Learning ability; distribution and quantitative analysis of AchE fibers; expression of nNOS in various cerebral areas. RESULTS: The twelve rats were all involved in the final analysis. ① Learning ability test: The learning abilities before operation in the experimental group [(14.67±4.97) times] were consistent with those in the control group [(14.33±4.32) times, P > 0.05], the learning abilities in the experimental group at 40 days after pinealectomy [(28.67±2.42) times] were obviously more than those before pinealectomy and those in the control group after operation [(13.83±8.33) times, P < 0.01]. ② Results of AchE-positive fibers density in cerebral cortex of rats: The AChE-positive fibers densities in motor and somatosensory cortex, CA1, CA2 and CA3 areas of hippocampus and in lamina multiforms of dentate gyrus in the experimental group were obviously lower than those in the control group [experimental group: (15 244±1 339), (14 764±1 391), (12 991±970), (15 077±1 020), (19 546±1 489), (19 337±1 378) μm2; control group: (21 001±1 021), (17 930±2 225), (17 260±1 342), (18 911±1 048), (24 108±1 671), (22 917±1 909) μm2, P < 0.01]. ③ Expression of nNOS in various cerebral areas: nNOS-positive cells in cerebral cortex of rats of the experimental group were more, furthermore the ones in somatosensory cortex were slightly more in motor cortex and the number (5.90±0.68) was more than that in the control group (3.68±0.39,P < 0.05). The nNOS-positive cells in SM-DB (16.21±2.03) were markedly more than those in the control group (9.32±1.05,P < 0.01). The nNOS-positive cells in hippocampus (4.27±0.75) and in corpus striatus (9.35±2.58) were not different with those in the control group (3.94±0.53, 8.96±2.31, P > 0.05). CONCLUSION: Decrease of melatonin due to pinealectomy of rats can result in learning disorder, which may be related to trauma of cholinergic neuron in cerebral cortex which were caused by nitric oxide neurotoxicity arose from the overexpression of nNOS in cerebral neocortex and SM-DB.
基金supported by the Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,Neuroscience Center,the China Human Brain Banking Consortiumsupported by the National Key R&D Program of China(Grant Nos.2016YFC1306300 and 2018YFC0910202)+10 种基金the National Natural Science Foundation of China(Grant Nos.30970650,31200614,31400669,81371515,81170665,and 81560121)Beijing Medical Research(Grant No.2018-7)Beijing Natural Science Foundation(Grant No.7173264 and 7172076)Beijing cooperative construction project(Grant No.110651103Beijing Science Program for the Top Young(Grant No.2015000021223TD04)Beijing Normal University(Grant No.11100704)Peking Union Medical College Hospital(Grant No.2016-2.27)CAMS Innovation Fund for Medical Sciences(Grant No.2017-I2M-1-009)the CAMS special basic research fund for central public research institutes(Grant No.2017PT310004)Biologic Medicine Information Center of ChinaNational Scientific Data Sharing Platform for Population and Health。
文摘The Brodmann area(BA)-based map is one of the most widely used cortical maps for studies of human brain functions and in clinical practice;however,the molecular architecture of BAs remains unknown.The present study provided a global multiregional proteomic map of the human cerebral cortex by analyzing 29 BAs.These 29 BAs were grouped into 6 clusters based on similarities in proteomic patterns:the motor and sensory cluster,vision cluster,auditory and Broca’s area cluster,Wernicke’s area cluster,cingulate cortex cluster,and heterogeneous function cluster.We identified 474 cluster-specific and 134 BA-specific signature proteins whose functions are closely associated with specialized functions and disease vulnerability of the corresponding cluster or BA.The findings of the present study could provide explanations for the functional connections between the anterior cingulate cortex and sensorimotor cortex and for anxiety-related function in the sensorimotor cortex.The brain transcriptome and proteome comparison indicates that they both could reflect the function of cerebral cortex,but show different characteristics.These proteomic data are publicly available at the Human Brain Proteome Atlas(www.brain-omics.com).Our results may enhance our understanding of the molecular basis of brain functions and provide an important resource to support human brain research.
基金the Natural Science Foundation of LiaoningProvince, No. 619019
文摘BACKGROUND: Immediate early gene (IEG) c-jun is a sensitive marker for functional status of nerve cells. Caspase-3 is a cysteine protease, which is a critical regulator of apoptosis. The effect of exogenous nerve growth factor (NGF) on the expression of c-jun mRNA and Caspase-3 protein in striate cortex of rats with transient global cerebral ischemia/reperfusion (IR) is unclear. OBJECTIVE: To study the protective effect of exogenous NGF on the brain of rats with transient global cerebral IR and its effecting pathway by observing the expression of c-jun mRNA and Caspase-3 protein. DESIGN: Randomized controlled animal trial. SETTING: Department of Neural Anatomy, Institute of Brain, China Medical University.MATERIALS:Eighteen healthy male SD rats of clean grade, aged 1 to 3 months, with body mass of 250 to 300 g, were involved in this study. NGF was provided by Dalian Svate Pharmaceutical Co.,Ltd. c-jun in situ hybridization detection kit, Caspase-3 antibody and SABC kit were purchased from Boster Biotechnology Co.,Ltd.METHODS: This trial was carried out in the Department of Neural Anatomy, Institute of Brain, China Medical University during September 2003 to April 2005. ① Experimental animals were randomized into three groups with 6 in each: sham-operation group, IR group and NGF group.②After the rats were anesthetized, the bilateral common carotid arteries and right external carotid arteries of rats were bluntly dissected and bilateral common carotid arteries were clamped for 30 minutes with bulldog clamps. Reperfusion began after buldog clamps were removed. Normal saline of 1mL and NGF (1×106 U/L) of 1 mL was injected into the common carotid artery of rats via right external carotid arteries in the IR group and NGF group respectively. The injection was conducted within 30 minutes, and then the right external carotid arteries were ligated. In the sham-operation group, occlusion of bilateral common carotid arteries and administration of drugs were omitted.③All the rats were executed by decollation at 3 hours after modeling. The animals were fixed with phosphate buffer solution (PBS, 0.1 mol/L) containing 40 g/L polyformaldehyde, their brains were quickly removed. The coronal section tissue mass containing striate cortex about 3 mm before line between two ears was taken and made into successive frozen sections.④The expression of c-jun mRNA and Caspase-3 protein in striate cortex of global cerebral ischemia rats were detected with in situ hybridization, immunohistochemistry and microscope image analysis. ⑤t test was used for comparing the difference of the measurement data.MAIN OUTCOME MEASURES:Comparison of the expression of IEG c-jun mRNA and Caspase-3 protein in striate cortex of brain of rats in each group.RESULTS:All the 18 SD rats were involved in the analysis of results. The c-jun mRNA and Caspase-3 protein positive reaction cells were found brown yellow in the striate cortex of rats, and most of them were in lamellas Ⅱ and Ⅲ, mainly presenting round or oval. The expression of c-jun mRNA and Caspase-3 protein in sham-operation group was weak or negative. The average gray value of c-jun mRNA and Caspase-3 protein in the IR group was significantly lower than that in the sham-operation group (49.52±4.13 vs. 95.48±5.28; 74.73±4.29 vs. 162.38±9.16,P < 0.01). The average gray value of c-jun mRNA and Caspase-3 protein in the NGF group was significantly higher than that in the IR group (63.96±4.25 vs.49.52±4.13; 83.98±4.13 vs. 74.73±4.29, P < 0.05). CONCLUSION: NGF can protect ischemic neurons by down-regulating the expression of c-jun mRNA and Caspase-3 protein in striate cortex of global cerebral ischemia rats.
基金several colleague therapists of the Rehabilitation Medicine Department of the Affiliated Hospital of Qingdao University of China for their support and selfless help
文摘Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons. However, there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function after cerebral infarction. We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function. This study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction. These patients were randomly assigned to three groups. The low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex(M1). The high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1. Finally, the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1. A total of 135 seconds of stimulation was applied in the sham group and high-frequency group. At 2 weeks after treatment, cortical latency of motor-evoked potentials and central motor conduction time were significantly lower compared with before treatment. Moreover, motor function scores were significantly improved. The above indices for the low- and high-frequency groups were significantly different compared with the sham group. However, there was no significant difference between the low- and high-frequency groups. The results show that low- and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction.
基金supported by grants from Hubei Provincial Natural Science Foundation of China(No.2019CFB805)National Natural Science Foundation of China(No.81670240 and No.81873467).
文摘Objective:To investigate glucose metabolic alterations in cerebral cortical subareas using ^(18)F-labeled glucose derivative fluorodeoxyglucose(FDG)micro-positron emission tomography(PET)scanning in a rat renal ischemia/reperfusion(RIR)model.Methods:Small-animal PET imaging in vivo was performed with ^(18)F-labeled FDG as a PET tracer to identify glucose metabolic alterations in cerebral cortical subregions using a rat model of RIR.Results:We found that the average standardized uptake value(SUV_(average))of the cerebral cortical subareas in the RIR group was significantly increased compared to the sham group(P<0.05).We also found that glucose uptake in different cortical subregions including the left auditory cortex,right medial prefrontal cortex,right para cortex,left retrosplenial cortex,right retrosplenial cortex,and right visual cortex was significantly increased in the RIR group(P<0.05),but there was no significant difference in the SUV_(avcrage) of right auditory cortex,left medial prefrontal cortex,left para cortex,and left visual cortex between the two groups.Conclusion:The ^(18)F-FDG PET data suggests that RIR causes a profound shift in the metabolic machinery of cerebral cortex subregions.
文摘Aging is a global phenomenon and a complex biological process of all living beings that introduces various changes.During this physiological process,the brain is the most affected organ due to changes in its structural and chemical functions,such as changes in plasticity and decrease in the number,diameter,length,and branching of dendrites and dendritic spines.Likewise,it presents a great reduction in volume resulting from the contraction of the gray matter.Consequently,aging can affect not only cognitive functions,including learning and memory,but also the quality of life of older people.As a result of the phenomena,various molecules with notable neuroprotective capacity have been proposed,which provide a therapeutic alternative for people under conditions of aging or some neurodegenerative diseases.It is important to indicate that in recent years the use of molecules with neurotrophic activity has shown interesting results when evaluated in in vivo models.This review aims to describe the neurotrophic potential of molecules such as resveratrol(3,5,4′-trihydroxystilbene),neurotrophins(brain-derived neurotrophic factor),and neurotrophic-type compounds such as the terminal carboxyl domain of the heavy chain of tetanus toxin,cerebrolysin,neuropeptide-12,and rapamycin.Most of these molecules have been evaluated by our research group.Studies suggest that these molecules exert an important therapeutic potential,restoring brain function in aging conditions or models of neurodegenerative diseases.Hence,our interest is in describing the current scientific evidence that supports the therapeutic potential of these molecules with active neurotrophic.
基金supported by the National Natural Science Foundation of China,No.81070523 and 81270728
文摘Neural stem/progenitor cell(NSC) transplantation has been shown to effectively improve neurological function in rats with hypoxic-ischemic brain damage.Vascular endothelial growth factor(VEGF) is a signaling protein that stimulates angiogenesis and improves neural regeneration.We hypothesized that transplantation of VEGF-transfected NSCs would alleviate hypoxic-ischemic brain damage in neonatal rats.We produced and transfected a recombinant lentiviral vector containing the VEGF165 gene into cultured NSCs.The transfected NSCs were transplanted into the left sensorimotor cortex of rats 3 days after hypoxic-ischemic brain damage.Compared with the NSCs group,VEGF m RNA and protein expression levels were increased in the transgene NSCs group,and learning and memory abilities were significantly improved at 30 days.Furthermore,histopathological changes were alleviated in these animals.Our findings indicate that transplantation of VEGF-transfected NSCs may facilitate the recovery of neurological function,and that its therapeutic effectiveness is better than that of unmodified NSCs.
文摘A review of recent animal models of Huntington’s disease showed many microRNAs had altered expression levels in the striatum and cerebral cortex,and which were mostly downregulated.Among the altered microRNAs were miR-9/9*,miR-29b,miR-124a,miR-132,miR-128,miR-139,miR-122,miR-138,miR-23b,miR-135b,miR-181(all downregulated)and miR-448(upregulated),and similar changes had been previously found in Huntington’s disease patients.In the animal cell studies,the altered microRNAs included miR-9,miR-9*,miR-135b,miR-222(all downregulated)and miR-214(upregulated).In the animal models,overexpression of miR-155 and miR-196a caused a decrease in mutant huntingtin mRNA and protein level,lowered the mutant huntingtin aggregates in striatum and cortex,and improved performance in behavioral tests.Improved performance in behavioral tests also occurred with overexpression of miR-132 and miR-124.In the animal cell models,overexpression of miR-22 increased the viability of rat primary cortical and striatal neurons infected with mutant huntingtin and decreased huntingtin-enriched foci of≥2μm.Also,overexpression of miR-22 enhanced the survival of rat primary striatal neurons treated with 3-nitropropionic acid.Exogenous expression of miR-214,miR-146a,miR-150,and miR-125b decreased endogenous expression of huntingtin mRNA and protein in HdhQ111/HdhQ111 cells.Further studies with animal models of Huntington’s disease are warranted to validate these findings and identify specific microRNAs whose overexpression inhibits the production of mutant huntingtin protein and other harmful processes and may provide a more effective means of treating Huntington’s disease in patients and slowing its progression.
基金supported by grants from the National Natural Science Foundation of China,No.31100769
文摘Platelet-derived growth factor receptor alpha(PDGFRα) is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whether there are differences in the distribution and morphology of oligodendrocyte precursor cells labeled by NG2 or PDGFRα in the developing neonatal rat brain remains unclear. In this study, by immunohistochemical staining, NG2 positive(NG2^+) cells were ubiquitous in the molecular layer, external pyramidal layer, internal pyramidal layer, and polymorphic layer of the cerebral cortex, and corpus callosum, external capsule, piriform cortex, and medial septal nucleus. NG2^+ cells were stellate or fusiform in shape with long processes that were progressively decreased and shortened over the course of brain development. The distribution and morphology of PDGFRα positive(PDGFRα^+) cells were coincident with NG2^+ cells. The colocalization of NG2 and PDGFRα in the cell bodies and processes of some cells was confirmed by double immunofluorescence labeling. Moreover, cells double-labeled for NG2 and PDGFRα were predominantly in the early postnatal stage of development. The numbers of NG2^+/PDGFRα^+ cells and PDGFRα^+ cells decreased, but the number of NG2^+ cells increased from postnatal days 3 to 14 in the developing brain. In addition, amoeboid microglial cells of the corpus callosum, newborn brain macrophages in the normal developing brain, did not express NG2 or PDGFRα, but NG2 expression was detected in amoeboid microglia after hypoxia. The present results suggest that NG2 and PDGFRα are specific markers of oligodendrocyte precursor cells at different stages during early development. Additionally, the NG2 protein is involved in inflammatory and pathological processes of amoeboid microglial cells.
文摘The neonatal hypoxic-ischemic encephalopathy(HIE)is an important cause of neurological morbidity and mortality in neonates.Cell therapy is considered a promising method for treating severe neurological disorders such as this one.Stem cells have the capacity for self-renewal and differentiation into certain cell lineages.The present study was aimed to find out the most beneficial route of bone marrow-derived mesenchymal stem cells(BMSCs)administration for the attenuation of experimentally induced HIE in neonatal rats.Sixty neonatal rats were divided randomly into four groups.Group 1:control group.Group 2:rats were exposed to bilateral ligation of cephalic arteries.Group 3:rats were exposed to bilateral ligation of cephalic arteries and then underwent intravenous(IV)BMSC injection.Group 4:rats were exposed to bilateral ligation of cephalic arteries and then underwent intracerebroventricular(ICV)BMSC injection.The animals were evaluated by(a)neurobehavioral tests;(b)histopathology,i.e.,histological and immuno-histochemical studies;and(3)gene expression studies.The BMSC treated groups(3 and 4)showed improvement in neurobehavioral tests,histopathological studies,and gene expression,as compared to non-injected lesioned rats(Group 2)with better improvement in Group 4(ICV injections)than in Group 3(IV injections).
文摘Visual information about an object is widely distributed over the cortex. The problem of how this information gets reassembled in consciousness is the “binding problem”. It is assumed in this paper that consciousness reads the distributed information as a laser reads a barcode;and that this solves the binding problem without resorting to oscillations, or synchronous signals, or any other form of mechanical association. Cortical distributions are made intelligible by consciousness that learns from childhood to recognize cortical arrays of single objects and project them onto the external world. An example shows how consciousness exercises its influence in the case of a well-known line drawing. When an object is constructed by consciousness there is no guarantee that the resulting image will be anything like the original object of observation. However, there is reason to believe that most of the visual images of our surroundings reflect real properties of those surroundings. These images have a constancy about them that is not always conveyed by the sensory input, but consistency in the external world can be learned by consciousness that is able to override the incongruities of the senses.
文摘The aim of this study was to investigate the role of endogenous enkephalin in the cerebral antihyperalgesic action of gabapentin.Neuropathic pain models and antihyperalgesic effect of gabapentin were confirmed by the presentation and changes of mechanical allodynia and thermal hyperalgesia of operated mouse hind paws.The results suggested that endogenous enkephalin may not be involved in the antihyperalgesic effect of gabapentin.
基金supported by grants from the National Natural Science Foundation of China(Grant No.2012CB966701)the Ministry of Science and Technology of the People’s Republic of China.
文摘Derived from neural stem cells(NSCs)and progenitor cells originated from the neuroectoderm,the nervous system presents an unprecedented degree of cellular diversity,interwoven to ensure correct connections for propagating information and responding to environ-mental cues.NSCs and progenitor cells must integrate cell-intrinsic programs and environmental cues to achieve production of appropriate types of neurons and glia at appropriate times and places during develop-ment.These developmental dynamics are reflected in changes in gene expression,which is regulated by transcription factors and at the epigenetic level.From early commitment of neural lineage to functional plas-ticity in terminal differentiated neurons,epigenetic regulation is involved in every step of neural develop-ment.Here we focus on the recent advance in our un-derstanding of epigenetic regulation on orderly genera-tion of diverse neural cell types in the mammalian nervous system,an important aspect of neural devel-opment and regenerative medicine.
基金This work was supported by grants from National Key Research and Development Program of China(2018YFA0108000)National Natural Science Foundation of China(31820103006,31630032,and 32070971)+1 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJ Lab,and Shanghai Center for Brain Science and Brain-Inspired Technology.We thank Dr.John L.Rubenstein for critical reading of the manuscript.
文摘Human cortical radial glial cells are primary neural stem cells that give rise to cortical glutaminergic projection pyramidal neurons, glial cells (oligodendrocytes and astrocytes) and olfactory bulb GABAergic interneurons. One of prominent features of the human cortex is enriched with glial cells, but there are major gaps in understanding how these glial cells are generated. Herein, by integrating analysis of published human cortical single-cell RNA-Seq datasets with our immunohistochemistical analyses, we show that around gestational week 18, EGFR-expressing human cortical truncated radial glial cells (tRGs) give rise to basal multipotent intermediate progenitors (bMIPCs) that express EGFR, ASCL1, OLIG2 and OLIG1. These bMIPCs undergo several rounds of mitosis and generate cortical oligodendrocytes, astrocytes and olfactory bulb interneurons. We also characterized molecular features of the cortical tRG. Integration of our findings suggests a general picture of the lineage progression of cortical radial glial cells, a fundamental process of the developing human cerebral cortex.
基金supported by grants from the National Key Research and Development Program of China(2018YFA0108000)the National Natural Science Foundation of China(31630032,31820103006,and 32070971)+1 种基金a Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJLab,and grants from NIH(R01MH094589 and R01NS089777)。
文摘Mouse cortical radial glial cells(RGCs)are primary neural stem cells that give rise to cortical oligodendrocytes,astrocytes,and olfactory bulb(OB)GABAergic interneurons in late embryogenesis.There are fundamental gaps in understanding how these diverse cell subtypes are generated.Here,by combining single-cell RNA-Seq with intersectional lineage analyses,we show that beginning at around E16.5,neocortical RGCs start to generate ASCL1^(+)EGFR^(+)apical multipotent intermediate progenitors(MIPCs),which then differentiate into basal MIPCs that express ASCL1,EGFR,OLIG2,and MKI67.These basal MIPCs undergo several rounds of divisions to generate most of the cortical oligodendrocytes and astrocytes and a subpopulation of OB interneurons.Finally,single-cell ATAC-Seq supported our model for the genetic logic underlying the specification and differentiation of cortical glial cells and OB interneurons.Taken together,this work reveals the process of cortical radial glial cell lineage progression and the developmental origins of cortical astrocytes and oligodendrocytes.
基金This work was supported by the National Key R&D Program of China(2018 YFF01012400)Jilin Provincial Middle and Young Scientific and Technological Innovation Talent and Team Project(20170519001JH)Program for JLU Science and Technology Innovative Research Team(2017TD-04).
文摘Research on the mechanical properties of brain tissue has received extensive attention.However,most of the current studies have been conducted at the phenomenological level.In this study,the indentation method was used to explore the difference in local mechanical properties among different regions of the porcine cerebral cortex.Further,hematoxylin-eosin and immunofluorescence staining methods were used to determine the correlation between the cellular density at different test points and mechanical properties of the porcine cerebral cortex.The frontal lobe exhibited the strongest viscosity.The temporal lobe displayed the lowest sensitivity to changes in the indentation speed,and the occipital lobe exhibited the highest shear modulus.Additionally,the shear modulus of different areas of the cerebral cortex was negatively correlated with the total number of local cells per unit area and positively correlated with the number of neuronal cell bodies per unit area.Exploration of the mechanical properties of the local brain tissue can provide basic data for the establishment of a finite element model of the brain and mechanical referential information for the implantation position of brain chips.
