Department of Pediatrics, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
Behav Brain Res. 2012 Feb 14;227(2):433-9. doi: 10.1016/j.bbr.2011.10.010. Epub 2011 Oct 14.
Newborn neurons derived from radial glia-like stem cells located in the dentate gyrus integrate into the adult hippocampal circuitry and participate in memory formation, spatial learning, pattern separation, fear conditioning, and anxiety. This process takes place throughout the life span of mammals, including humans; however, it follows a sharp declining curve. New neurons are generated abundantly during youth but very scarcely in the aged brain. The absolute number of newly generated neurons, or neurogenic output, is determined at different levels along the neurogenic cascade: the activation of quiescent stem cells; the mitotic potential of proliferating precursors; and the survival of neuronal fate-committed precursors. A continuous depletion of the hippocampal neural stem cell pool has been recently proposed as the main force underlying the age-related decline of neurogenesis, in contrast to the previous view of population of neural stem cells whose number remains constant but loses its ability to bear fruit. Nevertheless, the diminished neurogenic output may be reflecting other phenomena such as decreased mitotic capability of proliferating progenitors, decreased survival or changes in differentiation. We describe herein the most important events in determining the amount of neurogenesis in the dentate gyrus and examine the literature to understand the effects of age throughout the cascade.
由齿状回中的放射状胶质样干细胞衍生的新生神经元整合到成年海马回路中，并参与记忆形成、空间学习、模式分离、恐惧条件反射和焦虑。这个过程发生在哺乳动物的整个生命周期中，包括人类；然而，它遵循着一条急剧下降的曲线。在青年时期，大量产生新神经元，但在老年大脑中却非常稀少。新神经元的绝对数量，或神经发生输出，在神经发生级联的不同水平上被决定：静止干细胞的激活；增殖前体细胞的有丝分裂潜力；以及神经元命运决定前体细胞的存活。最近有人提出，海马神经干细胞池的持续耗竭是导致神经发生与年龄相关下降的主要原因，这与以前认为神经干细胞数量保持不变但丧失其产生果实的能力的观点相反。然而，神经发生输出的减少可能反映了其他现象，如增殖祖细胞的有丝分裂能力下降、存活或分化变化。本文描述了决定齿状回神经发生量的最重要事件，并查阅文献了解整个级联过程中的年龄效应。
