Stromal cell-derived factor-1 and its receptor CXCR4 are essential regulators of the neurogenesis that occurs in the adult hippocampal dentate gyrus.However,the effects of CXCR7,a new atypical receptor of stromal cell...Stromal cell-derived factor-1 and its receptor CXCR4 are essential regulators of the neurogenesis that occurs in the adult hippocampal dentate gyrus.However,the effects of CXCR7,a new atypical receptor of stromal cell-derived factor-1,on hippocampal neurogenesis after a stroke remain largely unknown.Our study is the first to investigate the effect of a CXCR7-neutralizing antibody on neurogenesis in the dentate gyrus and the associated recovery of cognitive function of rats in the chronic stage of cerebral ischemia.The rats were randomly divided into sham,sham+anti-CXCR7,ischemia and ischemia+anti-CXCR7 groups.Endothelin-1 was injected in the ipsilateral motor cortex and striatum to induce focal cerebral ischemia.Sham group rats were injected with saline instead of endothelin-1 via intracranial injection.Both sham and ischemic rats were treated with intraventricular infusions of CXCR7-neutralizing antibodies for 6 days 1 week after surgery.Immunofluorescence staining with doublecortin,a marker for neuronal precursors,was performed to assess the neurogenesis in the dentate gyrus.We found that anti-CXCR7 antibody infusion enhanced the proliferation and dendritic development of doublecortin-labeled cells in the dentate gyrus in both ischemic and sham-operated rats.Spatial learning and memory functions were assessed by Morris water maze tests 30-32 days after ischemia.CXCR7-neutralizing antibody treatment significantly reduced the escape latency of the spatial navigation trial and increased the time spent in the target quadrant of spatial probe trial in animals that received ischemic insult,but not in sham operated rats.These results suggest that CXCR7-neutralizing antibody enhances the neurogenesis in the dentate gyrus and improves the cognitive function after cerebral ischemia in rats.All animal experimental protocols and procedures were approved by the Institutional Animal Care and Use Committee of China Medical University(CMU16089 R)on December 8,2016.展开更多
目的探讨知母皂苷B（Saponins from Anemarrhena asphodeloides Bge，SAaB）对体外培养大鼠乳鼠大脑皮层神经元树突发育的促进作用。方法选用出生0～24h的Sprague—Dawley（SD）大鼠乳鼠，取皮层神经元进行体外细胞培养，培养4d的神经...目的探讨知母皂苷B（Saponins from Anemarrhena asphodeloides Bge，SAaB）对体外培养大鼠乳鼠大脑皮层神经元树突发育的促进作用。方法选用出生0～24h的Sprague—Dawley（SD）大鼠乳鼠，取皮层神经元进行体外细胞培养，培养4d的神经元用于实验。应用倒置相差显微镜测量培养神经元树突分支总长度（TDBL）、一级树突数目（PDN）、最大分支级数（MBO）和神经元胞体面积。Western印迹法观察神经元突触素蛋白表达的改变。结果形态学观察结果显示SAaB（10、30、100μmol／L）可明显促进树突发育，表现为树突分支总长度增加、一级树突数目增多、最大分支级数增大及胞体面积增大。并呈明显浓度依赖。Western印迹结果显示SAaB（10、30、100μmol／L）也可明显增加突触素蛋白表达水平，并呈明显浓度依赖。结论SAaB对体外培养皮层神经元树突的发育有促进作用。展开更多
基金supported by the National Natural Science Foundation of China,No.81401002(to SSZ)
文摘Stromal cell-derived factor-1 and its receptor CXCR4 are essential regulators of the neurogenesis that occurs in the adult hippocampal dentate gyrus.However,the effects of CXCR7,a new atypical receptor of stromal cell-derived factor-1,on hippocampal neurogenesis after a stroke remain largely unknown.Our study is the first to investigate the effect of a CXCR7-neutralizing antibody on neurogenesis in the dentate gyrus and the associated recovery of cognitive function of rats in the chronic stage of cerebral ischemia.The rats were randomly divided into sham,sham+anti-CXCR7,ischemia and ischemia+anti-CXCR7 groups.Endothelin-1 was injected in the ipsilateral motor cortex and striatum to induce focal cerebral ischemia.Sham group rats were injected with saline instead of endothelin-1 via intracranial injection.Both sham and ischemic rats were treated with intraventricular infusions of CXCR7-neutralizing antibodies for 6 days 1 week after surgery.Immunofluorescence staining with doublecortin,a marker for neuronal precursors,was performed to assess the neurogenesis in the dentate gyrus.We found that anti-CXCR7 antibody infusion enhanced the proliferation and dendritic development of doublecortin-labeled cells in the dentate gyrus in both ischemic and sham-operated rats.Spatial learning and memory functions were assessed by Morris water maze tests 30-32 days after ischemia.CXCR7-neutralizing antibody treatment significantly reduced the escape latency of the spatial navigation trial and increased the time spent in the target quadrant of spatial probe trial in animals that received ischemic insult,but not in sham operated rats.These results suggest that CXCR7-neutralizing antibody enhances the neurogenesis in the dentate gyrus and improves the cognitive function after cerebral ischemia in rats.All animal experimental protocols and procedures were approved by the Institutional Animal Care and Use Committee of China Medical University(CMU16089 R)on December 8,2016.
文摘目的探讨知母皂苷B（Saponins from Anemarrhena asphodeloides Bge，SAaB）对体外培养大鼠乳鼠大脑皮层神经元树突发育的促进作用。方法选用出生0～24h的Sprague—Dawley（SD）大鼠乳鼠，取皮层神经元进行体外细胞培养，培养4d的神经元用于实验。应用倒置相差显微镜测量培养神经元树突分支总长度（TDBL）、一级树突数目（PDN）、最大分支级数（MBO）和神经元胞体面积。Western印迹法观察神经元突触素蛋白表达的改变。结果形态学观察结果显示SAaB（10、30、100μmol／L）可明显促进树突发育，表现为树突分支总长度增加、一级树突数目增多、最大分支级数增大及胞体面积增大。并呈明显浓度依赖。Western印迹结果显示SAaB（10、30、100μmol／L）也可明显增加突触素蛋白表达水平，并呈明显浓度依赖。结论SAaB对体外培养皮层神经元树突的发育有促进作用。
