Dranovsky Alex, Hen René
Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, New York 10032, USA.
Biol Psychiatry. 2006 Jun 15;59(12):1136-43. doi: 10.1016/j.biopsych.2006.03.082.
Accumulating evidence implicates hippocampal neurogenesis in the pathophysiology of depression. Psychosocial stress reduces neurogenesis in rodents, whereas chronic treatment with antidepressants increases neurogenesis and blocks the effects of stress. The effects of stress and antidepressant treatment on hippocampal neurogenesis parallel behavioral changes in animal models. Moreover, ablating hippocampal neurogenesis renders antidepressants inactive in behavioral paradigms used to model antidepressant response and anxiety-like behavior in mice. In humans, monoamine-modulating antidepressants demonstrate clinical efficacy in treating depression and anxiety, which are often precipitated by psychosocial stress. This review examines the mounting evidence that stress and antidepressant treatment regulate neurogenesis in animals. Special attention is paid to the cellular and molecular mechanisms by which this regulation takes place. An analysis of current animal models used to study response to stress and antidepressants indicates the importance of modeling chronic treatment, which reflects both changes in neurogenesis and clinical response. Exploring responses of hippocampal neurogenesis to experimental challenges in appropriate animal models should delineate the role of adult-born neurons in hippocampal physiology. Focusing on neurogenic response to experimental paradigms of stress and antidepressant treatment is particularly interesting for understanding the pathophysiology of major depressive disorder.
越来越多的证据表明海马体神经发生与抑郁症的病理生理学有关。社会心理应激会减少啮齿动物的神经发生，而抗抑郁药的长期治疗会增加神经发生并阻断应激的影响。应激和抗抑郁药治疗对海马体神经发生的影响与动物模型中的行为变化相似。此外，消除海马体神经发生会使抗抑郁药在用于模拟小鼠抗抑郁反应和焦虑样行为的行为范式中失去活性。在人类中，调节单胺的抗抑郁药在治疗通常由社会心理应激引发的抑郁症和焦虑症方面显示出临床疗效。本综述探讨了越来越多的证据，即应激和抗抑郁药治疗在动物中调节神经发生。特别关注这种调节发生的细胞和分子机制。对目前用于研究对应激和抗抑郁药反应的动物模型的分析表明了模拟长期治疗的重要性，这反映了神经发生的变化和临床反应。在适当的动物模型中探索海马体神经发生对实验挑战的反应，应该能够阐明成年新生神经元在海马体生理学中的作用。关注对应激和抗抑郁药治疗实验范式的神经源性反应，对于理解重度抑郁症的病理生理学特别有意义。
