The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly f...The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area.However,only a small percentage of these neurons survive,and many do not reach the damaged area,possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex.A second major obstacle to stem cell therapy is the strong inflammatory reaction induced by cerebral ischemia,whereby the associated phagocytic activity of brain macrophages removes both therapeutic cells and/or cell-based drug carriers.To address these issues,neurogenesis was electrically stimulated in the subventricular zone,followed by isolation of proliferating cells,including newly formed neurons,which were subsequently mixed with a nutritional hydrogel.This mixture was then transferred to the stroke cavity of day 14 post-stroke mice.We found that the performance of the treated animals improved in behavioral tests,including novel object,open field,hole board,grooming,and“time-to-feel”adhesive tape tests.Furthermore,immunostaining revealed that the stem cell marker nestin,the neuroepithelial marker Mash1,and the immature neuronal marker doublecortin-positive cells survived in the transplanted area for 2 weeks,possibly due to reduced phagocytic activity and supportive angiogenesis.These results clearly indicate that the transplantation of committed subventricular zone stem cells combined with a protective nutritional gel directly into the infarct cavity after the peak of stroke-induced neuroinflammation represents a feasible approach to improve neurorestoration after cerebral ischemia.展开更多
The number and diversity of inhibitory neurons(INs)increased substantially during mammalian brain evolution.However,the generative mechanisms of the vast repertoire of human INs remain elusive.We performed spatial and...The number and diversity of inhibitory neurons(INs)increased substantially during mammalian brain evolution.However,the generative mechanisms of the vast repertoire of human INs remain elusive.We performed spatial and single-cell transcriptomics of human medial ganglionic eminence(hMGE),a pivotal source of cortical and subpallial INs,and built the trajectories of hMGE-derived cells during brain development.We identified spatiotemporally and molecularly segregated progenitor cell populations fated to produce distinct IN types.展开更多
Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential ...Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats (7 days old) subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2'-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2'- deoxyuddine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.展开更多
Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relations...Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus.Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats.Two months after injection,olfactory sensitivity was decreased in diabetic rats.Meanwhile,the number of Brd U-positive and Brd U+/DCX+double-labeled cells was lower in the subventricular zone of diabetic rats compared with agematched normal rats.Western blot results revealed downregulated expression of insulin receptorβ,phosphorylated glycogen synthase kinase 3β,and β-catenin in the subventricular zone of diabetic rats.Altogether,these results indicate that diabetes mellitus causes insulin deficiency,which negatively regulates glycogen synthase kinase 3β and enhances β-catenin degradation,with these changes inhibiting neural stem cell proliferation.Further,these signaling pathways affect proliferation and differentiation of neural stem cells in the subventricular zone.Dysfunction of subventricular zone neural stem cells causes a decline in olfactory bulb structural plasticity and impairs olfactory sensitivity in diabetic rats.展开更多
The subcellular localization of N-methyI-D-aspartic acid receptor subunit 1 in neural stem cells of the subventricular zone of adult rats was detected using electron microscopy, following immunohistochemistry and immu...The subcellular localization of N-methyI-D-aspartic acid receptor subunit 1 in neural stem cells of the subventricular zone of adult rats was detected using electron microscopy, following immunohistochemistry and immunogold-silver double staining. Results confirmed the presence of neural stem cells in the subventricular zone, which is a key neurogenic region in the central nervous system of adult mammals. The expression of N-methyI-D-aspartic acid receptor subunit 1 was higher than that of nestin and mainly distributed in the cell membrane, cytoplasm, rough endoplasmic reticulum and Golgi complex of neural stem cells.展开更多
Objective To analyze proliferation and differentiation of glial fibrillary acid protein(GFAP)-and nestin-positive(GFAP+estin+)cells isolated from the subventricular zone following fluid percussion brain injury to dete...Objective To analyze proliferation and differentiation of glial fibrillary acid protein(GFAP)-and nestin-positive(GFAP+estin+)cells isolated from the subventricular zone following fluid percussion brain injury to determine whether GFAP+estin+cells exhibit characteristics of neural stem cells.Methods Male Sprague-Dawley rats,aged 12 weeks and weighing 200-250 g,were randomly and evenly assigned to normal control group and model group.In the model group,a rat model of fluid percussion brain injury was established.Five days later,subventricular zone tissue was resected from each group and made into single cell suspension.After serum-free neural stem cell medium culture and subsequent serum-induced differentiation,cell type,proliferation and differentiation capacities were determined by immunofluorescence staining and flow cytometry.Results At 3-7 days after fluid percussion brain injury,nestin+/GFAP+cells in the single cell suspension from the model group significantly outnumbered those from the normal control group(P<0.01).In the model group,an increased number of small neurospheres with smooth cell edge and bulged center formed after primary culture,and were clearly visible with the increase of culture time and medium replacement.After several passages,many clonal spheres were obtained,suggesting strong self-proliferatiing capacity.Neurospheres from the model group differentiated into astrocytes,neurons and oligodendrocytes.Conclusion GFAP+estin+cells isolated from the adult rat subventricular zone after fluid percussion brain injury are thought to be neural stem cells because of their self-renewal and multi-differentiation capacities.展开更多
The subventricular zone (SVZ) is a region surrounding the lateral ventricles thatcontains neural stem cells and neural progenitor cells, which can proliferate and differentiateinto various neural and glial cells. SVZ ...The subventricular zone (SVZ) is a region surrounding the lateral ventricles thatcontains neural stem cells and neural progenitor cells, which can proliferate and differentiateinto various neural and glial cells. SVZ cells play important roles in neurological diseases likeneurodegeneration, neural injury, and glioblastoma multiforme. Investigating the anatomy,structure, composition, physiology, disease associations, and related mechanisms of SVZ is significant for neural stem cell therapy and treatment/prevention of neurological disorders. However, challenges remain regarding the mechanisms regulating SVZ cell proliferation,differentiation, and migration, delivering cells to damaged areas, and immune responses.In-depth studies of SVZ functions and related therapeutic developments may provide new insights and approaches for treating brain injuries and degenerative diseases, as well as a scientific basis for neural stem cell therapy. This review summarizes research findings on SVZ andneurological diseases to provide references for relevant therapies.展开更多
The adult subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal dentate gyrus(DG)are the two brain regions where neurogenesis occurs throughout life in the adult mammalian brain(Min...The adult subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal dentate gyrus(DG)are the two brain regions where neurogenesis occurs throughout life in the adult mammalian brain(Ming and Song,2011).Adult quiescent hippocampal neural stem cells(NSCs)are bona fide stem cells and,when activated,give rise to newborn granule neurons in the adult brain,which play vital roles in learning,memory,mood,and affective cognition(Bonaguidi et al.,2011;Ming and Song,2011).展开更多
MicroRNAs regulate neural stem cell function.Argonaute 2 protein,constituent of the RNA-induced silencing complex,plays an important role in regulating microRNA function for post-transcriptional gene silencing.Althoug...MicroRNAs regulate neural stem cell function.Argonaute 2 protein,constituent of the RNA-induced silencing complex,plays an important role in regulating microRNA function for post-transcriptional gene silencing.Although Argonaute 2 and microRNAs are recognized as central regulators of RNA-induced silencing complex,their precise role in adult neural stem cell function has remained unclear.In particular,it was not known whether Argonaute 2 is required for sustaining neural stem cell proliferation,neurogenesis,and oligodendrogenesis in the adult brain,or how its loss might influence recovery after ischemic injury.The present study examined the effect of Argonaute 2 deletion in adult neural stem cells on neurogenesis and oligodendrogenesis.Adult transgenic mice with conditional and inducible ablation of Argonaute 2 in Ascl1-lineage neural stem cells exhibited the reduction of neurogenesis in the ventricular-subventricular zone of the lateral ventricle and in the subgranular zone of the dentate gyrus,as evidenced by a decrease in neural stem cell proliferation and neuroblast numbers.Argonaute 2 deletion also reduced oligodendrogenesis in the corpus callosum,as indicated by the reduction of oligodendrocyte progenitor cell proliferation and the number of mature oligodendrocytes.Additionally,deleting Argonaute 2 in adult neural stem cells of ischemic mice exacerbated impairments of sensorimotor and cognitive functions.Mechanistically,Argonaute 2 ablation in neural stem cells reduced the stability of mature microRNAs and downregulated genes involved in the Shh(Sonic Hedgehog),Notch,and TGFβ(transforming growth factor beta)signaling pathways,which regulate the functions of neural stem cells.Collectively,our study demonstrates that Argonaute 2 is essential for adult neural stem cell-mediated neurogenesis and oligodendrogenesis,with its deletion worsening recovery after ischemia.By revealing that Argonaute 2 stabilizes mature microRNAs,our work uncovers a novel mechanism of neural stem cell regulation and highlights Argonaute 2 as a potential therapeutic target for neurodegenerative and ischemic brain diseases.展开更多
Background Functional electrical stimulation (FES) is known to promote the recovery of motor function in rats with ischemia and to upregulate the expression of growth factors which support brain neurogenesis.In this...Background Functional electrical stimulation (FES) is known to promote the recovery of motor function in rats with ischemia and to upregulate the expression of growth factors which support brain neurogenesis.In this study,we investigated whether postischemic FES could improve functional outcomes and modulate neurogenesis in the subventricular zone (SVZ) after focal cerebral ischemia.Methods Adult male Sprague-Dawley rats with permanent middle cerebral artery occlusion (MCAO) were randomly assigned to the control group,the placebo stimulation group,and the FES group.The rats in each group were further assigned to one of four therapeutic periods (1,3,7,or 14 days).FES was delivered 48 hours after the MCAO procedure and divided into two 10-minute sessions on each day of treatment with a 10-minute rest between them.Two intraperitoneal injections of bromodeoxyuridine (BrdU) were given 4 hours apart every day beginning 48 hours after the MCAO.Neurogenesis was evaluated by immunofluorescence staining.Wnt-3 which is strongly implicated in the proliferation and differentiation of neural stem cells (NSCs) was investigated by Western blotting analysis.The data wera subjected to oneway analysis of variance (ANOVA),followed by a Tukey/Kramer or Dunnett post hoc test.Results FES significantly increased the number of BrdU-positive cells and BrdU/glial flbrillary acidic protein doublepositive neural progenitor cells in the SVZ on days 7 and 14 of the treatment (P 〈0.05).The number of BrdU/doublecortin (DCX) double-positive migrating neuroblast cells in the ipsilateral SVZ on day 14 of the FES treatment group ((522.77±33.32) cells/mm2) was significantly increased compared with the control group ((262.58±35.11) cells/mm2,P 〈0.05) and the placebo group ((266.17±47.98) cells/mm2,P 〈0.05).However,only a few BrdUeuron-specific nuclear protein-positive cells were observed by day 14 of the treatment.At day 7,Wnt-3 was upregulated in the ipsilateral SVZs of the rats receiving FES ((0.44±0.05)%) compared with those of the control group rats ((0.31±0.02)%,P 〈0.05) or the placebo group rats ((0.31±0.04)%,P 〈0.05).At day 14,the corresponding values were (0.56±0.05)% in the FES group compared with those of the control group rats ((0.50±0.06)%,P 〈0.05) or the placebo group rats ((0.48±0.06)%,P 〈0.05).Conclusion FES augments the proliferation,differentiation,and migration of NSCs and thus promotes neurogenesis,which may be related to the improvement of neurological outcomes.展开更多
Adult neurogenesis is generally considered to be very limited;however,there is increasing evidence that this phenomenon is conserved across species.Traditionally,research has focused on identifying precursor cells,tho...Adult neurogenesis is generally considered to be very limited;however,there is increasing evidence that this phenomenon is conserved across species.Traditionally,research has focused on identifying precursor cells,those that are actively dividing or have the potential to divide.Direct evidence of adult neurogenesis has been found in rats,mice,songbirds,and nonhuman primates.In humans,while the evidence is indirect,it strongly suggests that neurogenesis also occurs during adulthood.In mammals,this active neurogenesis is preserved by radial glial progenitors,which remain in specific niches in the subventricular zone of the lateral ventricles and in the subgranular zone of the hippocampal dentate gyrus(Kumar et al.,2019).展开更多
The traditional Chinese medicine Buyang Huanwu Decoction has been shown to improve the neu- rological function of patients with stroke. However, the precise mechanisms underlying its effect remain poorly understood. I...The traditional Chinese medicine Buyang Huanwu Decoction has been shown to improve the neu- rological function of patients with stroke. However, the precise mechanisms underlying its effect remain poorly understood. In this study, we established a rat model of cerebral ischemia by middle cerebral artery occlusion and intragastrically administered 5 g/kg Buyang Huanwu Decoction, once per day, for 1, 7, 14 and 28 days after cerebral ischemia. Immunohistochemical staining revealed a number of cells positive for the neural stem cell marker nestin in the cerebral cortex, the subven- tricular zone and the ipsilateral hippocampal dentate gyrus in rat models of cerebral ischemia. Buyang Huanwu Decoction significantly increased the number of cells positive for 5-bromodeoxyuridine (BrdU), a cell proliferation-related marker, microtubule-associated protein-2, a marker of neuronal differentiation, and growth-associated protein 43, a marker of synaptic plasticity in the ischemic rat cerebral regions. The number of positive cells peaked at 14 and 28 days after intragastric administration of Buyang Huanwu Decoction. These findings suggest that Buyang Huanwu Decoction can promote the proliferation and differentiation of neural stem cells and en- hance synaptic plasticity in ischemic rat brain tissue.展开更多
The ginkgo biloba extract EGb761 improves memory loss and cognitive impairments in patients with senile dementia. It also promotes proliferation of neural stem cells in the subventricular zone in Parkinson's disease ...The ginkgo biloba extract EGb761 improves memory loss and cognitive impairments in patients with senile dementia. It also promotes proliferation of neural stem cells in the subventricular zone in Parkinson's disease model mice and in the hippocampal zone of young epileptic rats. However, it remains unclear whether EGb761 enhances proliferation of endogenous neural stem cells in the brain of rats with vascular dementia. In this study, a vascular dementia model was established by repeatedly clipping and reperfusing the bilateral common carotid arteries of rats in combination with an intraperitoneal injection of a sodium nitroprusside solution. Seven days after establishing the model, rats were intragastrically given EGb761 at 50 mg/kg per day. Learning and memory abilities were assessed using the Morris water maze and proliferation of endogenous neural stem cells in the subventricular zone and dentate gyrus were labeled by 5-bromo-2-deoxyuridine immunofluorescence in all rats at 15 days, and 1, 2, and 4 months after model establishment. The escape latencies in Morris water maze tests of rats with vascular dementia after EGb761 treatment were significantly shorter than the model group. Immunofluorescence staining showed that the number and proliferation of 5-bromo-2-deoxyuridine-positive cells in the subventricular zone and dentate gyrus of the EGb761-treated group were significantly higher than in the model group. These experimental findings suggest that EGb761 enhances proliferation of neural stem cells in the subventricular zone and dentate gyrus, and significantly improves learning and memory in rats with vascular dementia.展开更多
It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous s...It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or renewed.Herein,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury.Central nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem cells.Because of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than neurons.Consequently,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function.Scientists have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming techniques.Used alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural circuit.Thus can integration re plenish lost neurons after central nervous system injury,by improving the local microenvironment.By regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons.This offers a novel approach for treating central nervous system injury.展开更多
Constraint-induced movement therapy after cerebral ischemia stimulates axonal growth by decreasing expression levels of Nogo-A,RhoA,and Rho-associated kinase(ROCK)in the ischemic boundary zone.However,it remains uncle...Constraint-induced movement therapy after cerebral ischemia stimulates axonal growth by decreasing expression levels of Nogo-A,RhoA,and Rho-associated kinase(ROCK)in the ischemic boundary zone.However,it remains unclear if there are any associations between the Nogo-A/RhoA/ROCK pathway and angiogenesis in adult rat brains in pathological processes such as ischemic stroke.In addition,it has not yet been reported whether constraint-induced movement therapy can promote angiogenesis in stroke in adult rats by overcoming Nogo-A/RhoA/ROCK signaling.Here,a stroke model was established by middle cerebral artery occlusion and reperfusion.Seven days after stroke,the following treatments were initiated and continued for 3 weeks:forced limb use in constraint-induced movement therapy rats(constraint-induced movement therapy group),intraperitoneal infusion of fasudil(a ROCK inhibitor)in fasudil rats(fasudil group),or lateral ventricular injection of NEP1-40(a specific antagonist of the Nogo-66 receptor)in NEP1-40 rats(NEP1-40 group).Immunohistochemistry and western blot assay results showed that,at 2 weeks after middle cerebral artery occlusion,expression levels of RhoA and ROCK were lower in the ischemic boundary zone in rats treated with NEP1-40 compared with rats treated with ischemiaeperfusion or constraint-induced movement therapy alone.However,at 4 weeks after middle cerebral artery occlusion,expression levels of RhoA and ROCK in the ischemic boundary zone were markedly decreased in the NEP1-40 and constraint-induced movement therapy groups,but there was no difference between these two groups.Compared with the ischemiaeperfusion group,modified neurological severity scores and foot fault scores were lower and time taken to locate the platform was shorter in the constraint-induced movement therapy and fasudil groups at 4 weeks after middle cerebral artery occlusion,especially in the constraint-induced movement therapy group.Immunofluorescent staining demonstrated that fasudil promoted an immune response of nerve-regeneration-related markers(BrdU in combination with CD31(platelet endothelial cell adhesion molecule),Nestin,doublecortin,NeuN,and glial fibrillary acidic protein)in the subventricular zone and ischemic boundary zone ipsilateral to the infarct.After 3 weeks of constraint-induced movement therapy,the number of regenerated nerve cells was noticeably increased,and was accompanied by an increased immune response of tight junctions(claudin-5),a pericyte marker(a-smooth muscle actin),and vascular endothelial growth factor receptor 2.Taken together,the results demonstrate that,compared with fasudil,constraint-induced movement therapy led to stronger angiogenesis and nerve regeneration ability and better nerve functional recovery at 4 weeks after cerebral ischemiaeperfusion.In addition,constraint-induced movement therapy has the same degree of inhibition of RhoA and ROCK as NEP1-40.Therefore,constraint-induced movement therapy promotes angiogenesis and neurogenesis after cerebral ischemiaeperfusion injury,at least in part by overcoming the Nogo-A/RhoA/ROCK signaling pathway.All protocols were approved by the Institutional Animal Care and Use Committee of China Medical University,China on December 9,2015(approval No.2015 PS326 K).展开更多
Intensive agriculture activities,industrialization and growing numbers of wastewater treatment plants along river banks collectively contribute to the elevated levels of neurotoxic pollutants in natural water reservoi...Intensive agriculture activities,industrialization and growing numbers of wastewater treatment plants along river banks collectively contribute to the elevated levels of neurotoxic pollutants in natural water reservoirs across Europe.We established an in vitro bioassay based upon neural stem cells isolated from the subventricular zone of the postnatal mouse to evaluate the neurotoxic potential of raw wastewater,treated sewage effluent,groundwater and drinking water.The toxic potential of water samples was evaluated employing viability,proliferation,differentiation and migration assays.We found that raw wastewater could reduce the viability and proliferation of neural stem cells,and decreased the neuronal and astrocyte differentiation,neuronal neurite growth,astrocyte growth and cell migration.Treated sewage water also showed inhibitory effects on cell proliferation and migration.Our results indicated that relatively high concentrations of nitrogenous substances,pesticides,mercuric compounds,bisphenol-A,and phthalates,along with some other pollutants in raw wastewater and treated sewage water,might be the reason for the neuroinhibitory effects of these water samples.Our model successfully predicted the neurotoxicity of water samples collected from different sources and also revealed that the incomplete removal of contaminants from wastewater can be problematic for the developing nervous system.The presented data also provides strong evidence that more effective treatments should be used to minimize the contamination of water before release into major water bodies which may be considered as water reservoirs for human usage in the future.展开更多
Traumatic brain injury (TBI) is the leading cause of death and disability of persons under 45 years old in the United States, affecting over 1.5 million individtials each year. It had been th ought that recovery fro...Traumatic brain injury (TBI) is the leading cause of death and disability of persons under 45 years old in the United States, affecting over 1.5 million individtials each year. It had been th ought that recovery from such injuries is severely limited due to the inability of the adult bra in to replace damaged neurons. However, recent studies indicate that the mature mammalian central nervous system (CNS) has the potential to replenish damaged neurons by proliferation and neuronal differentiation of adult neural stem/progenitor cells residing in the neurogenic regions in the brain. Furthermore, increasing evidence indicates that these endogenous stem/ progenitor cells may play regenerative and reparative roles in response to CNS injuries or diseases. In support of this notion, heightened levels of cell proliferation and neurogenesis have been ob- served in response to brain trauma or insults suggesting that the brain has the inherent potential to restore populations of damaged or destroyed neurons. This review will discuss the potential functions of adult neurogenesis and recent development of strategies aiming at harnessing this neurogenic capacity in order to repopulate and repair the injured brain.展开更多
To date, complex components of available reagents have been used for directional induction of neural stem cells into dopaminergic neurons, resulting in a poor ability to repeat experiments. This study sought to invest...To date, complex components of available reagents have been used for directional induction of neural stem cells into dopaminergic neurons, resulting in a poor ability to repeat experiments. This study sought to investigate whether a homogenate of the substantia nigra of adult rats and/or basic fibroblast growth factor could directionally induce neural stem cells derived from the subventricular zone of embryonic rats to differentiate into dopaminergic neurons. Tyrosine hydroxylase-positive cells were observed exclusively after induction with the homogenate supernatant of the substantia nigra from adult rats and basic fibroblast growth factor for 48 hours in vitro. However, in the groups treated with homogenate supernatant or basic fibroblast growth factor alone, tyrosine hydroxylase expression was not observed. Moreover, the content of dopamine in the culture medium of subventricular zone neurons was significantly increased at 48 hours after induction with the homogenate supernatant of the substantia nigra from adult rats and basic fibroblast growth factor. Experimental findings indicate that the homogenate supernatant of the substantia nigra from adult rats and basic fibroblast growth factor could directionally induce neural stem cells derived from the subventricular zone of embryonic rats to differentiate into dopaminergic neurons in the substantia nigra with the ability to secrete dopamine.展开更多
基金supported by European Union Funding Programme,PNRR,No. 760058(to DMH)the UEFISCDI Project,No. PN-III-P4-IDPCE-2020-059(to APW)
摘要The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area.However,only a small percentage of these neurons survive,and many do not reach the damaged area,possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex.A second major obstacle to stem cell therapy is the strong inflammatory reaction induced by cerebral ischemia,whereby the associated phagocytic activity of brain macrophages removes both therapeutic cells and/or cell-based drug carriers.To address these issues,neurogenesis was electrically stimulated in the subventricular zone,followed by isolation of proliferating cells,including newly formed neurons,which were subsequently mixed with a nutritional hydrogel.This mixture was then transferred to the stroke cavity of day 14 post-stroke mice.We found that the performance of the treated animals improved in behavioral tests,including novel object,open field,hole board,grooming,and“time-to-feel”adhesive tape tests.Furthermore,immunostaining revealed that the stem cell marker nestin,the neuroepithelial marker Mash1,and the immature neuronal marker doublecortin-positive cells survived in the transplanted area for 2 weeks,possibly due to reduced phagocytic activity and supportive angiogenesis.These results clearly indicate that the transplantation of committed subventricular zone stem cells combined with a protective nutritional gel directly into the infarct cavity after the peak of stroke-induced neuroinflammation represents a feasible approach to improve neurorestoration after cerebral ischemia.
摘要The number and diversity of inhibitory neurons(INs)increased substantially during mammalian brain evolution.However,the generative mechanisms of the vast repertoire of human INs remain elusive.We performed spatial and single-cell transcriptomics of human medial ganglionic eminence(hMGE),a pivotal source of cortical and subpallial INs,and built the trajectories of hMGE-derived cells during brain development.We identified spatiotemporally and molecularly segregated progenitor cell populations fated to produce distinct IN types.
基金supported by Guangdong Province Science Research Project,No.B30502
摘要Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats (7 days old) subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2'-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2'- deoxyuddine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.
基金partly supported by the National Natural Science Foundation of China,No.81370448,81570725
摘要Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus.Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats.Two months after injection,olfactory sensitivity was decreased in diabetic rats.Meanwhile,the number of Brd U-positive and Brd U+/DCX+double-labeled cells was lower in the subventricular zone of diabetic rats compared with agematched normal rats.Western blot results revealed downregulated expression of insulin receptorβ,phosphorylated glycogen synthase kinase 3β,and β-catenin in the subventricular zone of diabetic rats.Altogether,these results indicate that diabetes mellitus causes insulin deficiency,which negatively regulates glycogen synthase kinase 3β and enhances β-catenin degradation,with these changes inhibiting neural stem cell proliferation.Further,these signaling pathways affect proliferation and differentiation of neural stem cells in the subventricular zone.Dysfunction of subventricular zone neural stem cells causes a decline in olfactory bulb structural plasticity and impairs olfactory sensitivity in diabetic rats.
基金the Natural Science Foundation of Universities in Jiangsu Province,No.07KJB310119the Natural Science Foundation of Jiangsu Province,No.BK2009087
摘要The subcellular localization of N-methyI-D-aspartic acid receptor subunit 1 in neural stem cells of the subventricular zone of adult rats was detected using electron microscopy, following immunohistochemistry and immunogold-silver double staining. Results confirmed the presence of neural stem cells in the subventricular zone, which is a key neurogenic region in the central nervous system of adult mammals. The expression of N-methyI-D-aspartic acid receptor subunit 1 was higher than that of nestin and mainly distributed in the cell membrane, cytoplasm, rough endoplasmic reticulum and Golgi complex of neural stem cells.
基金supported by the National Natural Science Foundation of China(No.30371442)New Teachers Foundation of Ministry of Education(No.20070698073)
摘要Objective To analyze proliferation and differentiation of glial fibrillary acid protein(GFAP)-and nestin-positive(GFAP+estin+)cells isolated from the subventricular zone following fluid percussion brain injury to determine whether GFAP+estin+cells exhibit characteristics of neural stem cells.Methods Male Sprague-Dawley rats,aged 12 weeks and weighing 200-250 g,were randomly and evenly assigned to normal control group and model group.In the model group,a rat model of fluid percussion brain injury was established.Five days later,subventricular zone tissue was resected from each group and made into single cell suspension.After serum-free neural stem cell medium culture and subsequent serum-induced differentiation,cell type,proliferation and differentiation capacities were determined by immunofluorescence staining and flow cytometry.Results At 3-7 days after fluid percussion brain injury,nestin+/GFAP+cells in the single cell suspension from the model group significantly outnumbered those from the normal control group(P<0.01).In the model group,an increased number of small neurospheres with smooth cell edge and bulged center formed after primary culture,and were clearly visible with the increase of culture time and medium replacement.After several passages,many clonal spheres were obtained,suggesting strong self-proliferatiing capacity.Neurospheres from the model group differentiated into astrocytes,neurons and oligodendrocytes.Conclusion GFAP+estin+cells isolated from the adult rat subventricular zone after fluid percussion brain injury are thought to be neural stem cells because of their self-renewal and multi-differentiation capacities.
基金supported by the Medical Scientific Research Foundation of Guangdong Province,China(No.A2022125,A2023486)the Medical Research Fund of the Qingyuan People’s Hospital(No.15001019002213)+1 种基金the National Natural Science Foundation of China(No.82203351)The Guangdong Basic and Applied Basic Research Foundation of China(No.2021A1515111095).
摘要The subventricular zone (SVZ) is a region surrounding the lateral ventricles thatcontains neural stem cells and neural progenitor cells, which can proliferate and differentiateinto various neural and glial cells. SVZ cells play important roles in neurological diseases likeneurodegeneration, neural injury, and glioblastoma multiforme. Investigating the anatomy,structure, composition, physiology, disease associations, and related mechanisms of SVZ is significant for neural stem cell therapy and treatment/prevention of neurological disorders. However, challenges remain regarding the mechanisms regulating SVZ cell proliferation,differentiation, and migration, delivering cells to damaged areas, and immune responses.In-depth studies of SVZ functions and related therapeutic developments may provide new insights and approaches for treating brain injuries and degenerative diseases, as well as a scientific basis for neural stem cell therapy. This review summarizes research findings on SVZ andneurological diseases to provide references for relevant therapies.
基金supported by National Institutes of Health(R35NS137480,R35NS116843,and RF1AG079557)by Dr.Miriam and Sheldon G.Adelson Medical Research Foundation.
摘要The adult subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal dentate gyrus(DG)are the two brain regions where neurogenesis occurs throughout life in the adult mammalian brain(Ming and Song,2011).Adult quiescent hippocampal neural stem cells(NSCs)are bona fide stem cells and,when activated,give rise to newborn granule neurons in the adult brain,which play vital roles in learning,memory,mood,and affective cognition(Bonaguidi et al.,2011;Ming and Song,2011).
基金supported by U.S.National Institutes of Health(NIH)National Institute of Diabetes and Digestive and Kidney Diseases(NIDDK)Diacomp Program grant 21AU4165(to XL)American Heart/Stroke Association Grant 18IPA34170331(to XL)。
摘要MicroRNAs regulate neural stem cell function.Argonaute 2 protein,constituent of the RNA-induced silencing complex,plays an important role in regulating microRNA function for post-transcriptional gene silencing.Although Argonaute 2 and microRNAs are recognized as central regulators of RNA-induced silencing complex,their precise role in adult neural stem cell function has remained unclear.In particular,it was not known whether Argonaute 2 is required for sustaining neural stem cell proliferation,neurogenesis,and oligodendrogenesis in the adult brain,or how its loss might influence recovery after ischemic injury.The present study examined the effect of Argonaute 2 deletion in adult neural stem cells on neurogenesis and oligodendrogenesis.Adult transgenic mice with conditional and inducible ablation of Argonaute 2 in Ascl1-lineage neural stem cells exhibited the reduction of neurogenesis in the ventricular-subventricular zone of the lateral ventricle and in the subgranular zone of the dentate gyrus,as evidenced by a decrease in neural stem cell proliferation and neuroblast numbers.Argonaute 2 deletion also reduced oligodendrogenesis in the corpus callosum,as indicated by the reduction of oligodendrocyte progenitor cell proliferation and the number of mature oligodendrocytes.Additionally,deleting Argonaute 2 in adult neural stem cells of ischemic mice exacerbated impairments of sensorimotor and cognitive functions.Mechanistically,Argonaute 2 ablation in neural stem cells reduced the stability of mature microRNAs and downregulated genes involved in the Shh(Sonic Hedgehog),Notch,and TGFβ(transforming growth factor beta)signaling pathways,which regulate the functions of neural stem cells.Collectively,our study demonstrates that Argonaute 2 is essential for adult neural stem cell-mediated neurogenesis and oligodendrogenesis,with its deletion worsening recovery after ischemia.By revealing that Argonaute 2 stabilizes mature microRNAs,our work uncovers a novel mechanism of neural stem cell regulation and highlights Argonaute 2 as a potential therapeutic target for neurodegenerative and ischemic brain diseases.
摘要Background Functional electrical stimulation (FES) is known to promote the recovery of motor function in rats with ischemia and to upregulate the expression of growth factors which support brain neurogenesis.In this study,we investigated whether postischemic FES could improve functional outcomes and modulate neurogenesis in the subventricular zone (SVZ) after focal cerebral ischemia.Methods Adult male Sprague-Dawley rats with permanent middle cerebral artery occlusion (MCAO) were randomly assigned to the control group,the placebo stimulation group,and the FES group.The rats in each group were further assigned to one of four therapeutic periods (1,3,7,or 14 days).FES was delivered 48 hours after the MCAO procedure and divided into two 10-minute sessions on each day of treatment with a 10-minute rest between them.Two intraperitoneal injections of bromodeoxyuridine (BrdU) were given 4 hours apart every day beginning 48 hours after the MCAO.Neurogenesis was evaluated by immunofluorescence staining.Wnt-3 which is strongly implicated in the proliferation and differentiation of neural stem cells (NSCs) was investigated by Western blotting analysis.The data wera subjected to oneway analysis of variance (ANOVA),followed by a Tukey/Kramer or Dunnett post hoc test.Results FES significantly increased the number of BrdU-positive cells and BrdU/glial flbrillary acidic protein doublepositive neural progenitor cells in the SVZ on days 7 and 14 of the treatment (P 〈0.05).The number of BrdU/doublecortin (DCX) double-positive migrating neuroblast cells in the ipsilateral SVZ on day 14 of the FES treatment group ((522.77±33.32) cells/mm2) was significantly increased compared with the control group ((262.58±35.11) cells/mm2,P 〈0.05) and the placebo group ((266.17±47.98) cells/mm2,P 〈0.05).However,only a few BrdUeuron-specific nuclear protein-positive cells were observed by day 14 of the treatment.At day 7,Wnt-3 was upregulated in the ipsilateral SVZs of the rats receiving FES ((0.44±0.05)%) compared with those of the control group rats ((0.31±0.02)%,P 〈0.05) or the placebo group rats ((0.31±0.04)%,P 〈0.05).At day 14,the corresponding values were (0.56±0.05)% in the FES group compared with those of the control group rats ((0.50±0.06)%,P 〈0.05) or the placebo group rats ((0.48±0.06)%,P 〈0.05).Conclusion FES augments the proliferation,differentiation,and migration of NSCs and thus promotes neurogenesis,which may be related to the improvement of neurological outcomes.
摘要Adult neurogenesis is generally considered to be very limited;however,there is increasing evidence that this phenomenon is conserved across species.Traditionally,research has focused on identifying precursor cells,those that are actively dividing or have the potential to divide.Direct evidence of adult neurogenesis has been found in rats,mice,songbirds,and nonhuman primates.In humans,while the evidence is indirect,it strongly suggests that neurogenesis also occurs during adulthood.In mammals,this active neurogenesis is preserved by radial glial progenitors,which remain in specific niches in the subventricular zone of the lateral ventricles and in the subgranular zone of the hippocampal dentate gyrus(Kumar et al.,2019).
基金supported by grants from the National Nature Science Foundation of China,No.30873355,81072939,81273989,81202694the Foundation of Educational Commission of Hunan Province in China,No.11C0954
摘要The traditional Chinese medicine Buyang Huanwu Decoction has been shown to improve the neu- rological function of patients with stroke. However, the precise mechanisms underlying its effect remain poorly understood. In this study, we established a rat model of cerebral ischemia by middle cerebral artery occlusion and intragastrically administered 5 g/kg Buyang Huanwu Decoction, once per day, for 1, 7, 14 and 28 days after cerebral ischemia. Immunohistochemical staining revealed a number of cells positive for the neural stem cell marker nestin in the cerebral cortex, the subven- tricular zone and the ipsilateral hippocampal dentate gyrus in rat models of cerebral ischemia. Buyang Huanwu Decoction significantly increased the number of cells positive for 5-bromodeoxyuridine (BrdU), a cell proliferation-related marker, microtubule-associated protein-2, a marker of neuronal differentiation, and growth-associated protein 43, a marker of synaptic plasticity in the ischemic rat cerebral regions. The number of positive cells peaked at 14 and 28 days after intragastric administration of Buyang Huanwu Decoction. These findings suggest that Buyang Huanwu Decoction can promote the proliferation and differentiation of neural stem cells and en- hance synaptic plasticity in ischemic rat brain tissue.
基金financially sponsored by the Natural Science Foundation of Shandong Province,No.Y2008C32Scientific Research Funds of Shandong Provincial Education Ministry,No.J01K09
摘要The ginkgo biloba extract EGb761 improves memory loss and cognitive impairments in patients with senile dementia. It also promotes proliferation of neural stem cells in the subventricular zone in Parkinson's disease model mice and in the hippocampal zone of young epileptic rats. However, it remains unclear whether EGb761 enhances proliferation of endogenous neural stem cells in the brain of rats with vascular dementia. In this study, a vascular dementia model was established by repeatedly clipping and reperfusing the bilateral common carotid arteries of rats in combination with an intraperitoneal injection of a sodium nitroprusside solution. Seven days after establishing the model, rats were intragastrically given EGb761 at 50 mg/kg per day. Learning and memory abilities were assessed using the Morris water maze and proliferation of endogenous neural stem cells in the subventricular zone and dentate gyrus were labeled by 5-bromo-2-deoxyuridine immunofluorescence in all rats at 15 days, and 1, 2, and 4 months after model establishment. The escape latencies in Morris water maze tests of rats with vascular dementia after EGb761 treatment were significantly shorter than the model group. Immunofluorescence staining showed that the number and proliferation of 5-bromo-2-deoxyuridine-positive cells in the subventricular zone and dentate gyrus of the EGb761-treated group were significantly higher than in the model group. These experimental findings suggest that EGb761 enhances proliferation of neural stem cells in the subventricular zone and dentate gyrus, and significantly improves learning and memory in rats with vascular dementia.
基金supported by the National Natural Science Foundation of ChinaNos.82272171 (to ZY),82271403 (to XL),31971279 (to ZY),81941011 (to XL),31730030 (to XL)。
摘要It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or renewed.Herein,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury.Central nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem cells.Because of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than neurons.Consequently,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function.Scientists have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming techniques.Used alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural circuit.Thus can integration re plenish lost neurons after central nervous system injury,by improving the local microenvironment.By regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons.This offers a novel approach for treating central nervous system injury.
基金supported by the National Natural Science Foundation of China(General Program),No.81771271(to JF)
摘要Constraint-induced movement therapy after cerebral ischemia stimulates axonal growth by decreasing expression levels of Nogo-A,RhoA,and Rho-associated kinase(ROCK)in the ischemic boundary zone.However,it remains unclear if there are any associations between the Nogo-A/RhoA/ROCK pathway and angiogenesis in adult rat brains in pathological processes such as ischemic stroke.In addition,it has not yet been reported whether constraint-induced movement therapy can promote angiogenesis in stroke in adult rats by overcoming Nogo-A/RhoA/ROCK signaling.Here,a stroke model was established by middle cerebral artery occlusion and reperfusion.Seven days after stroke,the following treatments were initiated and continued for 3 weeks:forced limb use in constraint-induced movement therapy rats(constraint-induced movement therapy group),intraperitoneal infusion of fasudil(a ROCK inhibitor)in fasudil rats(fasudil group),or lateral ventricular injection of NEP1-40(a specific antagonist of the Nogo-66 receptor)in NEP1-40 rats(NEP1-40 group).Immunohistochemistry and western blot assay results showed that,at 2 weeks after middle cerebral artery occlusion,expression levels of RhoA and ROCK were lower in the ischemic boundary zone in rats treated with NEP1-40 compared with rats treated with ischemiaeperfusion or constraint-induced movement therapy alone.However,at 4 weeks after middle cerebral artery occlusion,expression levels of RhoA and ROCK in the ischemic boundary zone were markedly decreased in the NEP1-40 and constraint-induced movement therapy groups,but there was no difference between these two groups.Compared with the ischemiaeperfusion group,modified neurological severity scores and foot fault scores were lower and time taken to locate the platform was shorter in the constraint-induced movement therapy and fasudil groups at 4 weeks after middle cerebral artery occlusion,especially in the constraint-induced movement therapy group.Immunofluorescent staining demonstrated that fasudil promoted an immune response of nerve-regeneration-related markers(BrdU in combination with CD31(platelet endothelial cell adhesion molecule),Nestin,doublecortin,NeuN,and glial fibrillary acidic protein)in the subventricular zone and ischemic boundary zone ipsilateral to the infarct.After 3 weeks of constraint-induced movement therapy,the number of regenerated nerve cells was noticeably increased,and was accompanied by an increased immune response of tight junctions(claudin-5),a pericyte marker(a-smooth muscle actin),and vascular endothelial growth factor receptor 2.Taken together,the results demonstrate that,compared with fasudil,constraint-induced movement therapy led to stronger angiogenesis and nerve regeneration ability and better nerve functional recovery at 4 weeks after cerebral ischemiaeperfusion.In addition,constraint-induced movement therapy has the same degree of inhibition of RhoA and ROCK as NEP1-40.Therefore,constraint-induced movement therapy promotes angiogenesis and neurogenesis after cerebral ischemiaeperfusion injury,at least in part by overcoming the Nogo-A/RhoA/ROCK signaling pathway.All protocols were approved by the Institutional Animal Care and Use Committee of China Medical University,China on December 9,2015(approval No.2015 PS326 K).
基金the Higher Education Commission(HEC),Pakistan(Ref.PD/OS-II/Batch-VI/Germany/2015/77159/17755)the University of Applied Sciences Kaiserslautern,Germany for providing financial support to execute the present project。
摘要Intensive agriculture activities,industrialization and growing numbers of wastewater treatment plants along river banks collectively contribute to the elevated levels of neurotoxic pollutants in natural water reservoirs across Europe.We established an in vitro bioassay based upon neural stem cells isolated from the subventricular zone of the postnatal mouse to evaluate the neurotoxic potential of raw wastewater,treated sewage effluent,groundwater and drinking water.The toxic potential of water samples was evaluated employing viability,proliferation,differentiation and migration assays.We found that raw wastewater could reduce the viability and proliferation of neural stem cells,and decreased the neuronal and astrocyte differentiation,neuronal neurite growth,astrocyte growth and cell migration.Treated sewage water also showed inhibitory effects on cell proliferation and migration.Our results indicated that relatively high concentrations of nitrogenous substances,pesticides,mercuric compounds,bisphenol-A,and phthalates,along with some other pollutants in raw wastewater and treated sewage water,might be the reason for the neuroinhibitory effects of these water samples.Our model successfully predicted the neurotoxicity of water samples collected from different sources and also revealed that the incomplete removal of contaminants from wastewater can be problematic for the developing nervous system.The presented data also provides strong evidence that more effective treatments should be used to minimize the contamination of water before release into major water bodies which may be considered as water reservoirs for human usage in the future.
摘要Traumatic brain injury (TBI) is the leading cause of death and disability of persons under 45 years old in the United States, affecting over 1.5 million individtials each year. It had been th ought that recovery from such injuries is severely limited due to the inability of the adult bra in to replace damaged neurons. However, recent studies indicate that the mature mammalian central nervous system (CNS) has the potential to replenish damaged neurons by proliferation and neuronal differentiation of adult neural stem/progenitor cells residing in the neurogenic regions in the brain. Furthermore, increasing evidence indicates that these endogenous stem/ progenitor cells may play regenerative and reparative roles in response to CNS injuries or diseases. In support of this notion, heightened levels of cell proliferation and neurogenesis have been ob- served in response to brain trauma or insults suggesting that the brain has the inherent potential to restore populations of damaged or destroyed neurons. This review will discuss the potential functions of adult neurogenesis and recent development of strategies aiming at harnessing this neurogenic capacity in order to repopulate and repair the injured brain.
基金sponsored by the General Program of Yunnan Provincial Application Basic Research, No. 2008ZC109M
摘要To date, complex components of available reagents have been used for directional induction of neural stem cells into dopaminergic neurons, resulting in a poor ability to repeat experiments. This study sought to investigate whether a homogenate of the substantia nigra of adult rats and/or basic fibroblast growth factor could directionally induce neural stem cells derived from the subventricular zone of embryonic rats to differentiate into dopaminergic neurons. Tyrosine hydroxylase-positive cells were observed exclusively after induction with the homogenate supernatant of the substantia nigra from adult rats and basic fibroblast growth factor for 48 hours in vitro. However, in the groups treated with homogenate supernatant or basic fibroblast growth factor alone, tyrosine hydroxylase expression was not observed. Moreover, the content of dopamine in the culture medium of subventricular zone neurons was significantly increased at 48 hours after induction with the homogenate supernatant of the substantia nigra from adult rats and basic fibroblast growth factor. Experimental findings indicate that the homogenate supernatant of the substantia nigra from adult rats and basic fibroblast growth factor could directionally induce neural stem cells derived from the subventricular zone of embryonic rats to differentiate into dopaminergic neurons in the substantia nigra with the ability to secrete dopamine.