Thomas Rosanne M, Hotsenpiller Gregory, Peterson Daniel A
Neural Repair and Neurogenesis Laboratory, Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064, USA.
J Neurosci. 2007 Mar 14;27(11):2734-43. doi: 10.1523/JNEUROSCI.3849-06.2007.
Factors modulating neurogenesis may contribute to the pathophysiology of affective disorders such as major depression. Environmental stressors in animal models have been proposed to alter neurogenesis, suggesting a mechanism for this contribution. The effect of an acute psychosocial stressor on either proliferation or survival (immediate, short term, and long term) was examined along with subsequent neuronal differentiation in the hippocampus of adult male Sprague Dawley rats. Subjects were exposed to a widely used social dominance paradigm that elicits behavioral and physiological responses to an acute psychosocial stressor. This social dominance paradigm may mimic human relational stress more realistically than laboratory stressors and provides a socially relevant model. We found that exposure to an acute psychosocial stressor at the time of cell generation resulted in a decreased number of newly generated cells in the hippocampus. By using sequential thymidine analog administration to provide temporal discrimination of DNA replication, we showed that short-term survival but not initial proliferation or immediate survival was altered in response to stress. Furthermore, we determined that stress experienced subsequent to proliferation also diminished long-term survival of cells. Thus, an acute episode of a social stress produces long-lasting effects on the incorporation of new hippocampal neurons by reducing their survival.
调节神经发生的因素可能在诸如重度抑郁症等情感障碍的病理生理学中发挥作用。动物模型中的环境应激源被认为会改变神经发生，这为上述作用机制提供了一种解释。本研究检测了急性心理社会应激源对成年雄性斯普拉格-道利大鼠海马体中增殖或存活（即刻、短期和长期）的影响，以及随后的神经元分化情况。实验对象暴露于一种广泛使用的社会优势范式下，该范式会引发对急性心理社会应激源的行为和生理反应。这种社会优势范式可能比实验室应激源更真实地模拟人类关系应激，并提供了一个与社会相关的模型。我们发现，在细胞生成时暴露于急性心理社会应激源会导致海马体中新生成细胞数量减少。通过连续给予胸腺嘧啶类似物以实现对DNA复制的时间分辨，我们发现，应激反应改变的是短期存活，而非初始增殖或即刻存活。此外，我们还确定，增殖后经历的应激也会降低细胞的长期存活。因此，社会应激的急性发作会通过减少新海马神经元的存活，对其整合产生持久影响。
