Objective: To investigate protective effects of Spilanthes acmella(S,acmella) Murr,extracts against pesticide-induced neuronal cells death and to elucidate the underlying molecular mechanism in dopaminergic(SH-SY5Y) c...Objective: To investigate protective effects of Spilanthes acmella(S,acmella) Murr,extracts against pesticide-induced neuronal cells death and to elucidate the underlying molecular mechanism in dopaminergic(SH-SY5Y) cells lines,Methods: Cell viability of SH-SY5 Y cells was studied by treating the cells with various concentration of pirimicarb for 24 hr,Neuroprotective effect of S,acmella Murr,extracts was investigated by adding the plant extracts to the medium for 24 hr prior to the incubation with 100 μM H_2O_2 or with pirimicarb for 24 hr,Control-untreated cells were incubated with the culture medium,Cell viability was measured by MTT assay,calpain and calpastatin expressions were analyzed by Western blotting and immunocytochemistry,Results: Pretreatment of SH-SY5 Y cells with S,acmella Murr,extracts(1 μg/m L) for 24 hr significantly increased the dopaminergic neurons in pirimicarb-induced neurotoxicity,In addition,pretreatment with the S,acmella Murr,extracts led to decreased calpain but increased calpastatin protein levels,Conclusion: S,acmella Murr,extracts exerted neuroprotective effect,via an alteration of calcium homeostasis,against pirimicarb induced neurotoxicity,The S,acmella Murr,might be a potential natural candidate with neuroprotective activity.展开更多
Amyloid beta(Aβ)precursor protein(APP)is a key protein in the pathogenesis of Alzheimer’s disease(AD).Both APP and its paralogue APLP1(amyloid beta precursor-like protein 1)have multiple functions in cell adhesion a...Amyloid beta(Aβ)precursor protein(APP)is a key protein in the pathogenesis of Alzheimer’s disease(AD).Both APP and its paralogue APLP1(amyloid beta precursor-like protein 1)have multiple functions in cell adhesion and proliferation.Previously it was thought that autophagy is a novel beta-amyloid peptide(Aβ)-generating pathway activated in AD.However,the protein proteolysis of APLP1 is still largely unknown.The present study shows that APLP1 is rapidly degraded in neuronal cells in response to stresses,such as proteasome inhibition.Activation of the endoplasmic reticulum(ER)stress by proteasome inhibitors induces autophagy,causing reduction of mature APLP1/APP.Blocking autophagy or JNK stress kinase rescues the protein expression for both APP and APLP1.Therefore,our results suggest that APP/APLP1 is degraded through autophagy and the APLP1 proteolysis is mainly mediated by autophagy-lysosome pathway.展开更多
Nicotine ingested from smoking exerts neuroprotection and developmental neurotoxicity in central nervous system.It can produce several changes of cognitive behaviors through regulating the release of different neurotr...Nicotine ingested from smoking exerts neuroprotection and developmental neurotoxicity in central nervous system.It can produce several changes of cognitive behaviors through regulating the release of different neurotransmitters in the brain.However,the effects of nicotine exposure or withdrawal on neurotransmitter metabolism of hippocampus are still unclear.In this study,we real-time evaluated the dynamic alterations in neurotransmitter metabolism of hippocampal neuronal(HT22)cells induced by nicotine exposure and withdrawal at relevant exposure levels of smoking and secondhand smoke by using a microfluidic chip-coupled with liquid chromatography-mass spectrometry(MC-LC-MS)system.We found HT22 cells mainly released related neurotransmitters of tryptophan and choline metabolism,both nicotine exposure and withdraw altered its neurotransmitters and their metabolites release.Exposure to nicotine mainly altered the secretion of serotonin,kynurenic acid,choline and acetylcholine of HT22 cells to improve hippocampal dependent cognition,and the change are closely related to the dose and duration of exposure.Moreover,the altered metabolites could rapidly recover after nicotine withdrawal,but picolinic acid was elevated.MC-LC-MS system used in present study showed a greater advantage to detect unstable metabolites than conventional method by using in vitro model,and the results of dynamic alterations of neurotransmitter metabolism induced by nicotine might provide a potential targets for drug development of neuroprotection or cognitive improvement.展开更多
Our previous study showed that cell cycle exit and neuronal differentiation 1(CEND1)may participate in neural stem cell cycle exit and oriented differentiation.However,whether CEND1-transfected neural stem cells can i...Our previous study showed that cell cycle exit and neuronal differentiation 1(CEND1)may participate in neural stem cell cycle exit and oriented differentiation.However,whether CEND1-transfected neural stem cells can improve the prognosis of traumatic brain injury remained unclear.In this study,we performed quantitative proteomic analysis and found that after traumatic brain injury,CEND1 expression was downregulated in mouse brain tissue.Three days after traumatic brain injury,we transplanted CEND1-transfected neural stem cells into the area surrounding the injury site.We found that at 5 weeks after traumatic brain injury,transplantation of CEND1-transfected neural stem cells markedly alleviated brain atrophy and greatly improved neurological function.In vivo and in vitro results indicate that CEND1 overexpression inhibited the proliferation of neural stem cells,but significantly promoted their neuronal differentiation.Additionally,CEND1 overexpression reduced protein levels of Notch1 and cyclin D1,but increased levels of p21 in CEND1-transfected neural stem cells.Treatment with CEND1-transfected neural stem cells was superior to similar treatment without CEND1 transfection.These findings suggest that transplantation of CEND1-transfected neural stem cells is a promising cell therapy for traumatic brain injury.This study was approved by the Animal Ethics Committee of the School of Biomedical Engineering of Shanghai Jiao Tong University,China(approval No.2016034)on November 25,2016.展开更多
Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a p...Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.展开更多
The sense of smell is important for human quality of life. This sophisticated sensorial system relies on the detection of odorant molecules that engage receptors expressed in the cilia of dedicated neurons that consti...The sense of smell is important for human quality of life. This sophisticated sensorial system relies on the detection of odorant molecules that engage receptors expressed in the cilia of dedicated neurons that constitute the olfactory epithelium(OE). Importantly, the OE is a highly active site of adult neurogenesis where short-lived neurons are efficiently replenished, even after massive neuronal cell loss. It is suggested that the degree of olfactory function recovery after OE injury may depend on the nature of the lesion(traumatic, chemical, infectious or inflammatory), as well on the velocity of cellular regeneration. Topical steroidal anti-inflammatory drugs, such as glucocorticoids, are routinely prescribed for treating upper airway inflammatory conditions, such as chronic rhinosinusitis. While the therapeutic strategy aims to minimize the inflammatory damage and dysfunction to nasal air conduction, new evidences raise concerns if such drugs may impair neuronal regeneration in the OE. In consequence, new directions are necessary in terms of drug development or prescription, in order to preserve olfactory function through lifelong repeated episodes of chronic inflammation in the upper respiratory tract. Here we discuss mechanisms involved in glucocorticoid deleterious effects to OE regeneration and possible therapeutic alternatives considering relevant side effects.展开更多
Spinal cord injury(SCI),either from trauma or degenerative changes,can res ult in severe disability and impaired quality of life.Understanding the cellular processes and molecular mechanisms that underlie SCI is imper...Spinal cord injury(SCI),either from trauma or degenerative changes,can res ult in severe disability and impaired quality of life.Understanding the cellular processes and molecular mechanisms that underlie SCI is imperative to identifying molecular targets for potential therapy.Recent studies have shown that non-coding RNAs,including both long non-coding RNAs(lncRNAs)and circular RNAs(circRNAs),regulate various cellular processes in SCI.In this review,we will describe the changes in lncRNA and circRNA expression that occur after SCI and how these changes may be related to SCI progression.Current evidence for the roles of lncRNAs and circRNAs in neuronal cell death and glial cell activation will also be reviewed.Finally,the possibility that lncRNAs and circRNAs are novel modulato rs of SCI pathogenesis will be discussed.展开更多
Retinal damage in the adult zebrafish induces Müller glia reprogramming to produce neuronal progenitor cells that proliferate and differentiate into retinal neurons.Notch signaling,which is a fundamental mechanis...Retinal damage in the adult zebrafish induces Müller glia reprogramming to produce neuronal progenitor cells that proliferate and differentiate into retinal neurons.Notch signaling,which is a fundamental mechanism known to drive cell-cell communication,is required to maintain Müller glia in a quiescent state in the undamaged retina,and repression of Notch signaling is necessary for Müller glia to reenter the cell cycle.The dynamic regulation of Notch signaling following retinal damage also directs proliferation and neurogenesis of the Müller glia-derived progenitor cells in a robust regeneration response.In contrast,mammalian Müller glia respond to retinal damage by entering a prolonged gliotic state that leads to additional neuronal death and permanent vision loss.Understanding the dynamic regulation of Notch signaling in the zebrafish retina may aid efforts to stimulate Müller glia reprogramming for regeneration of the diseased human retina.Recent findings identified DeltaB and Notch3 as the ligand-receptor pair that serves as the principal regulators of zebrafish Müller glia quiescence.In addition,multi-omics datasets and functional studies indicate that additional Notch receptors,ligands,and target genes regulate cell proliferation and neurogenesis during the regeneration time course.Still,our understanding of Notch signaling during retinal regeneration is limited.To fully appreciate the complex regulation of Notch signaling that is required for successful retinal regeneration,investigation of additional aspects of the pathway,such as post-translational modification of the receptors,ligand endocytosis,and interactions with other fundamental pathways is needed.Here we review various modes of Notch signaling regulation in the context of the vertebrate retina to put recent research in perspective and to identify open areas of inquiry.展开更多
Hypoxia conditioning could increase the survival of transplanted neuronal progenitor cells(NPCs)in rats with cerebral ischemia but could also hinder neuronal differentiation partly by suppressing mitochondrial metabol...Hypoxia conditioning could increase the survival of transplanted neuronal progenitor cells(NPCs)in rats with cerebral ischemia but could also hinder neuronal differentiation partly by suppressing mitochondrial metabolism.In this work,the mitochondrial metabolism of hypoxia-conditioned NPCs(hcNPCs)was upregulated via the additional administration of resveratrol,an herbal compound,to resolve the limitation of hypoxia conditioning on neuronal differentiation.Resveratrol was first applied during the in vitro neuronal differentiation of hcNPCs and concurrently promoted the differentiation,synaptogenesis,and functional development of neurons derived from hcNPCs and restored the mitochondrial metabolism.Furthermore,this herbal compound was used as an adjuvant during hcNPC transplantation in a photothrombotic stroke rat model.Resveratrol promoted neuronal differentiation and increased the long-term survival of transplanted hcNPCs.18-fluorine fluorodeoxyglucose positron emission tomography and rotarod test showed that resveratrol and hcNPC transplantation synergistically improved the neurological and metabolic recovery of stroke rats.In conclusion,resveratrol promoted the neuronal differentiation and therapeutic efficiency of hcNPCs in stroke rats via restoring mitochondrial metabolism.This work suggested a novel approach to promote the clinical translation of NPC transplantation therapy.展开更多
The process of cortical expansion in the central nerv-ous system is a key step of mammalian brain devel-opment to ensure its physiological function.Radial glial(RG)cells are a glial cell type contributing to this pro-...The process of cortical expansion in the central nerv-ous system is a key step of mammalian brain devel-opment to ensure its physiological function.Radial glial(RG)cells are a glial cell type contributing to this pro-gress as intermediate neural progenitor cells responsi-ble for an increase in the number of cortical neurons.In this review,we discuss the current understanding of RG cells during neurogenesis and provide further in-formation on the mechanisms of neurodevelopmental diseases and stem cell-related brain tumorigenesis.Knowledge of neuronal stem cell and relative diseases will bridge benchmark research through translational studies to clinical therapeutic treatments of these dis-eases.展开更多
The present study explores the neuroprotective effects of the natural food product Cinnamomum cassia or Cinnamon(CIN)on lithium pilocarpine(Li-Pc)induced SE in experimental rats to look into a possibility of it being ...The present study explores the neuroprotective effects of the natural food product Cinnamomum cassia or Cinnamon(CIN)on lithium pilocarpine(Li-Pc)induced SE in experimental rats to look into a possibility of it being used as antiepileptic drug.Recent studies have shown significant potential of pharmacological,prophylactic or therapeutic use of CIN in many beneficial activities in the body.The animals received CIN pre-treatment before induction of SE.Besides the severity of the seizures,other parameters like cognitive behavioral dysfunction,hippocampal oxidative stress and histological abnormalities in the hippocampus of animals induced with SE by lithium(Li)in 3 mEq/ml/kg dose,i.p.followed 20 h later by pilocarpine(Pc)in 20 mg/ml/kg dose,s.c.CIN was administered intraperitoneally at the doses of 25 and 50 mg/mL/kg,30 minutes before Pc injection.Mortality(if any)within 24 hours was also recorded.Ethical approval was obtained from the Ethics Committee Review Board of the College of Pharmacy of King Saud University,Riyadh,Saudi Arabia.Treatment with CIN significantly ameliorated the frequency and severity of epileptic seizures in a dose-dependent manner.The cognitive dysfunctions were improved,hippocampal oxidative stress was ameliorated and neuronal cell loss in the hippocampus were also attenuated significantly and dose-dependently by CIN.Possible therapeutic application of CIN as an antiepileptic and as an antioxidant for the treatment of SE has a great potential and warrants further studies.展开更多
Oxidative stress influences cell survival and homeostasis, but the mechanisms underlying the biological effects of oxidative stress remain to be elucidated. We have defined that the
Autism spectrum disorder(ASD)is a neurological disorder in which a significant number of children experience a developmental regression characterized by a loss of previously-acquired skills and abilities.Loss of neuro...Autism spectrum disorder(ASD)is a neurological disorder in which a significant number of children experience a developmental regression characterized by a loss of previously-acquired skills and abilities.Loss of neurological function in ASD,as observed in affected children who have regressed,can be explained as neurodegeneration.Although there is research evidence of neurodegeneration or progressive encephalopathy in ASD,the issue of neurodegeneration in ASD is still under debate.Evidence of neurodegeneration in the brain in ASD includes:(1)neuronal cell loss,(2)activated microglia and astrocytes,(3)proinflammatory cytokines,(4)oxidative stress,and(5)elevated 8-oxo-guanosine levels.The evidence from this review suggests that neurodegeneration underlies the loss of neurological function in children with ASD who have experienced regression and loss of previously acquired skills and abilities,and that research into treatments to address the issue of neurodegeneration in ASD are warranted.展开更多
This review summarizes the data on the functional significance of ubiquitous(NKCC1)and renal-specific(NKCC2)isoforms of electroneutral sodium,potassium and chloride cotransporters.These carriers contribute to the path...This review summarizes the data on the functional significance of ubiquitous(NKCC1)and renal-specific(NKCC2)isoforms of electroneutral sodium,potassium and chloride cotransporters.These carriers contribute to the pathogenesis of hypertension via regulation of intracellular chloride concentration in vascular smooth muscle and neuronal cells and via sensing chloride concentration in the renal tubular fluid,respectively.Both NKCC1 and NKCC2 are inhibited by furosemide and other high-ceiling diuretics widely used for attenuation of extracellular fluid volume.However,the chronic usage of these compounds for the treatment of hypertension and other volume-expanded disorders may have diverse side-effects due to suppression of myogenic response in microcirculatory beds.展开更多
基金supported by Mahidol University and the Thailand Research Fund(TRF)under a research grant for new scholar(MRG5980032)to WSby the office of the Higher Education Commission,Mahidol University,under the National Research Universities Initiative
文摘Objective: To investigate protective effects of Spilanthes acmella(S,acmella) Murr,extracts against pesticide-induced neuronal cells death and to elucidate the underlying molecular mechanism in dopaminergic(SH-SY5Y) cells lines,Methods: Cell viability of SH-SY5 Y cells was studied by treating the cells with various concentration of pirimicarb for 24 hr,Neuroprotective effect of S,acmella Murr,extracts was investigated by adding the plant extracts to the medium for 24 hr prior to the incubation with 100 μM H_2O_2 or with pirimicarb for 24 hr,Control-untreated cells were incubated with the culture medium,Cell viability was measured by MTT assay,calpain and calpastatin expressions were analyzed by Western blotting and immunocytochemistry,Results: Pretreatment of SH-SY5 Y cells with S,acmella Murr,extracts(1 μg/m L) for 24 hr significantly increased the dopaminergic neurons in pirimicarb-induced neurotoxicity,In addition,pretreatment with the S,acmella Murr,extracts led to decreased calpain but increased calpastatin protein levels,Conclusion: S,acmella Murr,extracts exerted neuroprotective effect,via an alteration of calcium homeostasis,against pirimicarb induced neurotoxicity,The S,acmella Murr,might be a potential natural candidate with neuroprotective activity.
基金supported by National Natural Science Foundation of China(Grant No.30900748).
文摘Amyloid beta(Aβ)precursor protein(APP)is a key protein in the pathogenesis of Alzheimer’s disease(AD).Both APP and its paralogue APLP1(amyloid beta precursor-like protein 1)have multiple functions in cell adhesion and proliferation.Previously it was thought that autophagy is a novel beta-amyloid peptide(Aβ)-generating pathway activated in AD.However,the protein proteolysis of APLP1 is still largely unknown.The present study shows that APLP1 is rapidly degraded in neuronal cells in response to stresses,such as proteasome inhibition.Activation of the endoplasmic reticulum(ER)stress by proteasome inhibitors induces autophagy,causing reduction of mature APLP1/APP.Blocking autophagy or JNK stress kinase rescues the protein expression for both APP and APLP1.Therefore,our results suggest that APP/APLP1 is degraded through autophagy and the APLP1 proteolysis is mainly mediated by autophagy-lysosome pathway.
基金the National Natural Science Foundation of China(No.22076197)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(No.YJKYYQ20200034)+2 种基金Shenzhen Engineering Laboratory of Single-molecule Detection and Instrument Development(No.XMHT20190204002)Shenzhen Science and Technology Innovation Commission(No.JCYJ20200109115405930)Basic and Applied Basic Research Foundation of Guangdong Province(No.2020B1515120080)。
文摘Nicotine ingested from smoking exerts neuroprotection and developmental neurotoxicity in central nervous system.It can produce several changes of cognitive behaviors through regulating the release of different neurotransmitters in the brain.However,the effects of nicotine exposure or withdrawal on neurotransmitter metabolism of hippocampus are still unclear.In this study,we real-time evaluated the dynamic alterations in neurotransmitter metabolism of hippocampal neuronal(HT22)cells induced by nicotine exposure and withdrawal at relevant exposure levels of smoking and secondhand smoke by using a microfluidic chip-coupled with liquid chromatography-mass spectrometry(MC-LC-MS)system.We found HT22 cells mainly released related neurotransmitters of tryptophan and choline metabolism,both nicotine exposure and withdraw altered its neurotransmitters and their metabolites release.Exposure to nicotine mainly altered the secretion of serotonin,kynurenic acid,choline and acetylcholine of HT22 cells to improve hippocampal dependent cognition,and the change are closely related to the dose and duration of exposure.Moreover,the altered metabolites could rapidly recover after nicotine withdrawal,but picolinic acid was elevated.MC-LC-MS system used in present study showed a greater advantage to detect unstable metabolites than conventional method by using in vitro model,and the results of dynamic alterations of neurotransmitter metabolism induced by nicotine might provide a potential targets for drug development of neuroprotection or cognitive improvement.
基金supported by the National Natural Science Foundation of China,No.81701895Shanghai Jiao Tong University Medicine-Engineering Research Fund,China,No.YG2016QN20(both to FY)。
文摘Our previous study showed that cell cycle exit and neuronal differentiation 1(CEND1)may participate in neural stem cell cycle exit and oriented differentiation.However,whether CEND1-transfected neural stem cells can improve the prognosis of traumatic brain injury remained unclear.In this study,we performed quantitative proteomic analysis and found that after traumatic brain injury,CEND1 expression was downregulated in mouse brain tissue.Three days after traumatic brain injury,we transplanted CEND1-transfected neural stem cells into the area surrounding the injury site.We found that at 5 weeks after traumatic brain injury,transplantation of CEND1-transfected neural stem cells markedly alleviated brain atrophy and greatly improved neurological function.In vivo and in vitro results indicate that CEND1 overexpression inhibited the proliferation of neural stem cells,but significantly promoted their neuronal differentiation.Additionally,CEND1 overexpression reduced protein levels of Notch1 and cyclin D1,but increased levels of p21 in CEND1-transfected neural stem cells.Treatment with CEND1-transfected neural stem cells was superior to similar treatment without CEND1 transfection.These findings suggest that transplantation of CEND1-transfected neural stem cells is a promising cell therapy for traumatic brain injury.This study was approved by the Animal Ethics Committee of the School of Biomedical Engineering of Shanghai Jiao Tong University,China(approval No.2016034)on November 25,2016.
基金supported by the National Key Research and Development Program of China,Nos.2017YFE0122900(to BH),2019YFA0110800(to WL),2019YFA0903802(to YW),2021YFA1101604(to LW),2018YFA0108502(to LF),and 2020YFA0804003(to JW)the National Natural Science Foundation of China,Nos.31621004(to WL,BH)and 31970821(to YW)+1 种基金CAS Project for Young Scientists in Basic Research,No.YSBR-041(to YW)Joint Funds of the National Natural Science Foundation of China,No.U21A20396(to BH)。
文摘Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.
基金supported by research grants to IG from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo(FAPESP 2007/53732-8)Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq 484869/2012-4)CEPID Redoxoma(FAPESP 2013/07937-8)
文摘The sense of smell is important for human quality of life. This sophisticated sensorial system relies on the detection of odorant molecules that engage receptors expressed in the cilia of dedicated neurons that constitute the olfactory epithelium(OE). Importantly, the OE is a highly active site of adult neurogenesis where short-lived neurons are efficiently replenished, even after massive neuronal cell loss. It is suggested that the degree of olfactory function recovery after OE injury may depend on the nature of the lesion(traumatic, chemical, infectious or inflammatory), as well on the velocity of cellular regeneration. Topical steroidal anti-inflammatory drugs, such as glucocorticoids, are routinely prescribed for treating upper airway inflammatory conditions, such as chronic rhinosinusitis. While the therapeutic strategy aims to minimize the inflammatory damage and dysfunction to nasal air conduction, new evidences raise concerns if such drugs may impair neuronal regeneration in the OE. In consequence, new directions are necessary in terms of drug development or prescription, in order to preserve olfactory function through lifelong repeated episodes of chronic inflammation in the upper respiratory tract. Here we discuss mechanisms involved in glucocorticoid deleterious effects to OE regeneration and possible therapeutic alternatives considering relevant side effects.
基金the National Natural Science Foundation of China,No.81901241(to YZ)。
文摘Spinal cord injury(SCI),either from trauma or degenerative changes,can res ult in severe disability and impaired quality of life.Understanding the cellular processes and molecular mechanisms that underlie SCI is imperative to identifying molecular targets for potential therapy.Recent studies have shown that non-coding RNAs,including both long non-coding RNAs(lncRNAs)and circular RNAs(circRNAs),regulate various cellular processes in SCI.In this review,we will describe the changes in lncRNA and circRNA expression that occur after SCI and how these changes may be related to SCI progression.Current evidence for the roles of lncRNAs and circRNAs in neuronal cell death and glial cell activation will also be reviewed.Finally,the possibility that lncRNAs and circRNAs are novel modulato rs of SCI pathogenesis will be discussed.
基金National Eye Institute R01-EY024519 and U01-EY027267(to DRH)the Center for Zebrafish Research,University of Notre Dame.
文摘Retinal damage in the adult zebrafish induces Müller glia reprogramming to produce neuronal progenitor cells that proliferate and differentiate into retinal neurons.Notch signaling,which is a fundamental mechanism known to drive cell-cell communication,is required to maintain Müller glia in a quiescent state in the undamaged retina,and repression of Notch signaling is necessary for Müller glia to reenter the cell cycle.The dynamic regulation of Notch signaling following retinal damage also directs proliferation and neurogenesis of the Müller glia-derived progenitor cells in a robust regeneration response.In contrast,mammalian Müller glia respond to retinal damage by entering a prolonged gliotic state that leads to additional neuronal death and permanent vision loss.Understanding the dynamic regulation of Notch signaling in the zebrafish retina may aid efforts to stimulate Müller glia reprogramming for regeneration of the diseased human retina.Recent findings identified DeltaB and Notch3 as the ligand-receptor pair that serves as the principal regulators of zebrafish Müller glia quiescence.In addition,multi-omics datasets and functional studies indicate that additional Notch receptors,ligands,and target genes regulate cell proliferation and neurogenesis during the regeneration time course.Still,our understanding of Notch signaling during retinal regeneration is limited.To fully appreciate the complex regulation of Notch signaling that is required for successful retinal regeneration,investigation of additional aspects of the pathway,such as post-translational modification of the receptors,ligand endocytosis,and interactions with other fundamental pathways is needed.Here we review various modes of Notch signaling regulation in the context of the vertebrate retina to put recent research in perspective and to identify open areas of inquiry.
基金This study was sponsored by the National Key Research and Development Program of China(No.2016YFA0100900)National Natural Science Foundation of China(NSFC)(Nos.81761148029,81725009,81900255,and 82030049)the Fund for Shanxi“1331 Project”Key Innovative Research Team.
文摘Hypoxia conditioning could increase the survival of transplanted neuronal progenitor cells(NPCs)in rats with cerebral ischemia but could also hinder neuronal differentiation partly by suppressing mitochondrial metabolism.In this work,the mitochondrial metabolism of hypoxia-conditioned NPCs(hcNPCs)was upregulated via the additional administration of resveratrol,an herbal compound,to resolve the limitation of hypoxia conditioning on neuronal differentiation.Resveratrol was first applied during the in vitro neuronal differentiation of hcNPCs and concurrently promoted the differentiation,synaptogenesis,and functional development of neurons derived from hcNPCs and restored the mitochondrial metabolism.Furthermore,this herbal compound was used as an adjuvant during hcNPC transplantation in a photothrombotic stroke rat model.Resveratrol promoted neuronal differentiation and increased the long-term survival of transplanted hcNPCs.18-fluorine fluorodeoxyglucose positron emission tomography and rotarod test showed that resveratrol and hcNPC transplantation synergistically improved the neurological and metabolic recovery of stroke rats.In conclusion,resveratrol promoted the neuronal differentiation and therapeutic efficiency of hcNPCs in stroke rats via restoring mitochondrial metabolism.This work suggested a novel approach to promote the clinical translation of NPC transplantation therapy.
基金supported by the National Basic Research Program of China(Grant No.2012CB966800)the 1000 Young Talents Program.
文摘The process of cortical expansion in the central nerv-ous system is a key step of mammalian brain devel-opment to ensure its physiological function.Radial glial(RG)cells are a glial cell type contributing to this pro-gress as intermediate neural progenitor cells responsi-ble for an increase in the number of cortical neurons.In this review,we discuss the current understanding of RG cells during neurogenesis and provide further in-formation on the mechanisms of neurodevelopmental diseases and stem cell-related brain tumorigenesis.Knowledge of neuronal stem cell and relative diseases will bridge benchmark research through translational studies to clinical therapeutic treatments of these dis-eases.
文摘The present study explores the neuroprotective effects of the natural food product Cinnamomum cassia or Cinnamon(CIN)on lithium pilocarpine(Li-Pc)induced SE in experimental rats to look into a possibility of it being used as antiepileptic drug.Recent studies have shown significant potential of pharmacological,prophylactic or therapeutic use of CIN in many beneficial activities in the body.The animals received CIN pre-treatment before induction of SE.Besides the severity of the seizures,other parameters like cognitive behavioral dysfunction,hippocampal oxidative stress and histological abnormalities in the hippocampus of animals induced with SE by lithium(Li)in 3 mEq/ml/kg dose,i.p.followed 20 h later by pilocarpine(Pc)in 20 mg/ml/kg dose,s.c.CIN was administered intraperitoneally at the doses of 25 and 50 mg/mL/kg,30 minutes before Pc injection.Mortality(if any)within 24 hours was also recorded.Ethical approval was obtained from the Ethics Committee Review Board of the College of Pharmacy of King Saud University,Riyadh,Saudi Arabia.Treatment with CIN significantly ameliorated the frequency and severity of epileptic seizures in a dose-dependent manner.The cognitive dysfunctions were improved,hippocampal oxidative stress was ameliorated and neuronal cell loss in the hippocampus were also attenuated significantly and dose-dependently by CIN.Possible therapeutic application of CIN as an antiepileptic and as an antioxidant for the treatment of SE has a great potential and warrants further studies.
文摘Oxidative stress influences cell survival and homeostasis, but the mechanisms underlying the biological effects of oxidative stress remain to be elucidated. We have defined that the
文摘Autism spectrum disorder(ASD)is a neurological disorder in which a significant number of children experience a developmental regression characterized by a loss of previously-acquired skills and abilities.Loss of neurological function in ASD,as observed in affected children who have regressed,can be explained as neurodegeneration.Although there is research evidence of neurodegeneration or progressive encephalopathy in ASD,the issue of neurodegeneration in ASD is still under debate.Evidence of neurodegeneration in the brain in ASD includes:(1)neuronal cell loss,(2)activated microglia and astrocytes,(3)proinflammatory cytokines,(4)oxidative stress,and(5)elevated 8-oxo-guanosine levels.The evidence from this review suggests that neurodegeneration underlies the loss of neurological function in children with ASD who have experienced regression and loss of previously acquired skills and abilities,and that research into treatments to address the issue of neurodegeneration in ASD are warranted.
基金This work was supported by grants from the Canadian Institutes for Health Research(MOP-81392)(S.N.O.)Russian Foundation for Fundamental Research##14-04-31705(S.V.K.),15-04-00101(S.N.O.)+1 种基金the Russian Scientific Foundation#14-15-00006(S.N.O.)the USA National Institutes of Health Award R01-GM85058(N.O.D.).
文摘This review summarizes the data on the functional significance of ubiquitous(NKCC1)and renal-specific(NKCC2)isoforms of electroneutral sodium,potassium and chloride cotransporters.These carriers contribute to the pathogenesis of hypertension via regulation of intracellular chloride concentration in vascular smooth muscle and neuronal cells and via sensing chloride concentration in the renal tubular fluid,respectively.Both NKCC1 and NKCC2 are inhibited by furosemide and other high-ceiling diuretics widely used for attenuation of extracellular fluid volume.However,the chronic usage of these compounds for the treatment of hypertension and other volume-expanded disorders may have diverse side-effects due to suppression of myogenic response in microcirculatory beds.
