Adult neurogenesis, cell cycle and drug discovery in psychiatry.
Adult neurogenesis, cell cycle and drug discovery in psychiatry.
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精神病学中的成人神经发生、细胞周期和药物发现。
DOI：
10.1038/npp.2008.164
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Chesnokova,Vera
中科院分区：
文献类型：
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作者：
Pechnick,RobertN;Chesnokova,Vera
多年来，哺乳动物大脑中新神经元的产生被认为是受发育限制的。现在很清楚，神经发生确实发生在成年哺乳动物中，包括人类（Eriksson et al, 1998）。抗抑郁药物和减轻抑郁的程序，如电休克和运动，会增加神经发生。成人神经发生、抗抑郁药物和抑郁症之间的关系引起了相当大的兴趣和争议（Duman, 2004； Scharfman和Hen， 2007）。p21Cip1是一种周期蛋白依赖性激酶抑制剂，抑制细胞周期的进展和增殖。它存在于海马体亚颗粒带的成神经细胞和新发育的神经元中（Pechnick et al, 2008）。三环抗抑郁药丙咪嗪的慢性治疗可降低p21Cip1转录物和蛋白水平，并刺激该区域的神经发生。此外，缺乏p21Cip1的小鼠海马神经发生率增加。因此，p21Cip1抑制海马神经发生，抗抑郁药诱导的神经发生刺激可能是由于p21Cip1表达降低。细胞周期调节发生在抗抑郁药主要作用部位的下游，这表明新的治疗策略可能直接针对细胞周期蛋白。
For many years the production of new neurons in mammalian brain was thought to be restricted to development. It is now clear that neurogenesis does occur in adult mammals, including humans (Eriksson et al, 1998). Antidepressant drugs and procedures that reduce depression, such as electroconvulsive shock and exercise, increase neurogenesis. The relationships among adult neurogenesis, antidepressant drugs, and depression have generated considerable interest and controversy (Duman, 2004; Scharfman and Hen, 2007).p21Cip1, a cyclin-dependent kinase inhibitor, restrains cell-cycle progression and proliferation. It is found in neuroblasts and newly developing neurons in the subgranular zone of the hippocampus (Pechnick et al, 2008). Chronic treatment with the tricyclic antidepressant imipramine decreases p21Cip1 transcript and protein levels and stimulates neurogenesis in this region. Moreover, mice lacking p21Cip1 have increased rates of hippocampal neurogenesis. Thus, p21Cip1 restrains neurogenesis in the hippocampus, and antidepressant-induced stimulation of neurogenesis might be due to decreased p21Cip1 expression. Cell-cycle regulation occurs downstream from the primary site of action of antidepressants, suggesting that new therapeutic strategies might directly target cell-cycle proteins.