The role of adult hippocampal neurogenesis underlying stress vulnerability

1)稳定剂、抗抑郁药和单胺类药物对成年大鼠齿状回神经干/祖细胞的影响为了评价稳定剂、抗抑郁药和单胺类药物对成年大鼠海马区神经发生的直接影响，建立了成年大鼠齿状回神经干/祖细胞的培养体系。糖皮质激素的血清水平在应激条件下升高，降低了细胞的增殖率。相反，锂和丙戊酸都恢复了糖皮质激素的作用。研究表明，β-连环蛋白/三氯甲烷体系在这些稳定剂的作用中起着重要作用。另一方面，包括SSRI和SNRI在内的抗抑郁药没有任何效果。去甲肾上腺素，而不是5-羟色胺，通过β-2受体以剂量依赖的方式增加细胞数量。这些结果提示抗抑郁药物以不同的方式增加了海马神经元的再生。2)HPA轴的活动与HIPPOAM…的关系更多的PAL体积。有令人信服的证据表明，HPA轴异常在情绪障碍的病理生理学中起着重要作用。此外，皮质醇水平升高导致CA3区海马神经元功能障碍，胞体缩小，齿状回神经发生减少。在本研究中，我们探讨了抑郁症患者经地塞米松(DEX)/促肾上腺皮质激素释放激素(CRH)联合试验评估的HPA异常与MRI手动分割测量的海马体积之间的关系。与对照组相比，抑郁症患者对DEX/CRH试验的垂体-肾上腺皮质反应显著增强。此外，患者的海马体体积明显减小。在联合地塞米松/促肾上腺皮质激素释放试验的任何时间点，皮质醇浓度〓为5μg/dl的“非抑制者”与“抑制者”相比，皮质醇浓度下降幅度更大。这些结果提示，HPA轴的异常可能与情绪障碍受试者的海马体体积减少有关。较少

1) The effect of stabilizers, antidepressants and monoamines to neural stem / progenitor cells derived from adult rat dentate gyrus.To evaluate the direct effect of stabilizers, antidepressants and monoamines to neurogenesis in the adult hippocampus, we established a culture system of neural stem / progenitor cells derived from adult rat dentate gyrus. Glucocorticoid of which serum level is increased under stress condition decreased a proliferation rate of the cells. On the contrary, both lithium and valproic acid recovered this glucocorticoid's effect. The β-catenin / TCF system was shown to play an important role in these stabilizer's action. On the other hand, antidepressants including SSRI and SNRI did not have any effects. Noradrenaline, but not serotonin, increased the cells thorough β 2 receptor with dose dependent manner. These results suggested antidepressants increased a hippocampal neurogenesis in various ways.2) The relationship between the activity of HPA axis and hippocam … More pal volume.There is compelling evidence for an important role of HPA axis abnormalities in the pathophysiology of mood disorders. Moreover, raised level of cortisol has been shown to produce the neuronal dysfunction of hippocampus with shrunken cell bodies in CA3 and decreased neurogenesis in dentate gyrus. In this study we investigated the relationship between the HPA abnormalities assessed with combined dexamethasone (DEX) / corticotropine-releasing hormone (CRH) test and hippocampal volume measured by manual segmentation on MRI in depressive patients. Significant enhanced pituitary-adrenocortical response to the DEX/CRH test were observed in depressive patients compared with controls. Moreover, hippocampal volume of patients was significantly decreased. The reduction was greater in 'nonsuppressor' who showed 〓 5μg/dl of cortisol concentration on any time points of combined DEX/CRH test compared with 'suppressors'. These results suggest that HPA axis abnormalities might be associated to the reduction of hippocampal volume in subjects suffered from mood disorder. Less