Objective Schizophrenia is a complex neuropsychiatric disorder characterized by cognitive,affective,and behavioral abnormalities.Existing treatments have yielded limited effects on improving cognitive function.Recent ...Objective Schizophrenia is a complex neuropsychiatric disorder characterized by cognitive,affective,and behavioral abnormalities.Existing treatments have yielded limited effects on improving cognitive function.Recent studies have identified the abnormal differentiation of hippocampal neural stem cells(NSCs),neuronal loss,and dysregulated proliferation of astrocytes as significant pathological mechanisms contributing to the symptoms of schizophrenia.Impaired hippocampal neurogenesis may lead to emotional and cognitive deficits and biases in learning and memory,indicating that NSC differentiation is critical.NEP1-40,a Nogo-A receptor inhibitor,has shown promise for nerve protection and repair promotion.However,the effects of NEP1-40 on stem cell differentiation,the reduction in neuronal apoptosis,and the amelioration of schizophrenia-like behaviors have not been adequately investigated.This study examined the influence of NEP1-40 on NSC differentiation,hippocampal neuronal apoptosis,and proliferation in adolescent mice,along with its potential to enhance cognitive and behavioral outcomes in MK-801-induced schizophrenia mouse models.Methods In in vivo experiments,a schizophrenia mouse model was successfully established.Subsequently,behavioral tests were conducted,followed by Western blotting(WB)and immunofluorescence(IF)analyses.In in vitro settings,NSCs were cultured and transfected.Flow cytometry,along with WB and IF assays,was employed to evaluate the effects of NEP1-40.Results Schizophrenia-like behaviors in mice were significantly improved with the overexpression of NEP1-40.Compared with the model group,the NEP1-40 treatment group presented increased expression of a neuronal marker(Tuj1),reduced expression of an astroglial marker(GFAP),and decreased hippocampal neuronal apoptosis.NSC differentiation was assessed by quantifying the number of BrdU-positive cells coexpressing Tuj1 and GFAP in the hippocampal dentate gyrus.NEP1-40 treatment led to an increase in BrdU/Tuj1-positive cells and a reduction in BrdU/GFAP-positive cells.In cellular studies,NEP1-40 overexpression similarly increased the number of Tuj1-positive cells,reduced the number of GFAP-positive cells,decreased the degree of neuronal apoptosis,and promoted neuronal proliferation.Conclusion These findings demonstrated the neurogenic effects of NEP1-40 on NSCs and their potential to mitigate schizophrenia-like behaviors in vivo.展开更多
文摘旨在探索山东省及其子区域植被净生态系统生产力(Net Ecosystem Productivity,NEP)的时空变化特征及其驱动因素,评估气温(TEM)、降水(PRE)和饱和蒸汽压差(VPD)等因素对植被NEP的影响。基于2000-2020年间的植被净初级生产力(Net Primary Productivity,NPP),采用土壤呼吸地统计(Geostatistical Model of Soil Respiration,GSMSR)模型、植被NEP估算模型和地理探测器工具,通过趋势分析、相关分析和差异分析等研究方法,开展深入研究。结果表明,1)山东省植被NEP在2000-2020年间整体呈上升趋势,空间分布特征表现为从东北向西南递减,沿海地区高于内陆地区。全省植被NEP的年平均值为87.0 g·m^(-2)·a^(-1)(以C计),且超过1/3的地区由碳源区域转变为碳汇区域。2)山东省大部分地区植被NEP与气温、降水呈正相关,与饱和蒸汽压差呈负相关,不同因子间的交互作用普遍对植被NEP的影响大于单一因子的影响。3)山东省4个子区域(鲁西、鲁东、鲁北、鲁中南)植被NEP的变化趋势存在明显的空间分异,鲁中南地区植被NEP增加最为显著,其次是鲁西和鲁东地区,而鲁北地区的增幅相对较小。该研究为深入理解区域生态系统的碳循环动态以及制定相应的生态保护策略提供了科学依据。
基金funded by Ningxia Natural Science Foundation(No.2022AAC03154).
文摘Objective Schizophrenia is a complex neuropsychiatric disorder characterized by cognitive,affective,and behavioral abnormalities.Existing treatments have yielded limited effects on improving cognitive function.Recent studies have identified the abnormal differentiation of hippocampal neural stem cells(NSCs),neuronal loss,and dysregulated proliferation of astrocytes as significant pathological mechanisms contributing to the symptoms of schizophrenia.Impaired hippocampal neurogenesis may lead to emotional and cognitive deficits and biases in learning and memory,indicating that NSC differentiation is critical.NEP1-40,a Nogo-A receptor inhibitor,has shown promise for nerve protection and repair promotion.However,the effects of NEP1-40 on stem cell differentiation,the reduction in neuronal apoptosis,and the amelioration of schizophrenia-like behaviors have not been adequately investigated.This study examined the influence of NEP1-40 on NSC differentiation,hippocampal neuronal apoptosis,and proliferation in adolescent mice,along with its potential to enhance cognitive and behavioral outcomes in MK-801-induced schizophrenia mouse models.Methods In in vivo experiments,a schizophrenia mouse model was successfully established.Subsequently,behavioral tests were conducted,followed by Western blotting(WB)and immunofluorescence(IF)analyses.In in vitro settings,NSCs were cultured and transfected.Flow cytometry,along with WB and IF assays,was employed to evaluate the effects of NEP1-40.Results Schizophrenia-like behaviors in mice were significantly improved with the overexpression of NEP1-40.Compared with the model group,the NEP1-40 treatment group presented increased expression of a neuronal marker(Tuj1),reduced expression of an astroglial marker(GFAP),and decreased hippocampal neuronal apoptosis.NSC differentiation was assessed by quantifying the number of BrdU-positive cells coexpressing Tuj1 and GFAP in the hippocampal dentate gyrus.NEP1-40 treatment led to an increase in BrdU/Tuj1-positive cells and a reduction in BrdU/GFAP-positive cells.In cellular studies,NEP1-40 overexpression similarly increased the number of Tuj1-positive cells,reduced the number of GFAP-positive cells,decreased the degree of neuronal apoptosis,and promoted neuronal proliferation.Conclusion These findings demonstrated the neurogenic effects of NEP1-40 on NSCs and their potential to mitigate schizophrenia-like behaviors in vivo.
