Chronic unpredictable stress decreases cell proliferation in the cerebral cortex of the adult rat
Chronic unpredictable stress decreases cell proliferation in the cerebral cortex of the adult rat
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DOI：
10.1016/j.biopsych.2007.02.006
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发表时间：
2007-09-01
影响因子：
10.6
通讯作者：
Duman, Ronald S.
中科院分区：
文献类型：
--
作者：
Banasr, Mounira;Valentine, Gerald W.;Duman, Ronald S.
背景：在抑郁症患者脑组织的尸检研究中，最一致的形态学发现之一是前额叶皮质神经胶质细胞的数量减少。方法：为了解决这个问题，我们将成年大鼠置于慢性应激(抑郁的易感因素)中，并测量了细胞增殖作为潜在的细胞机制，这可能是导致抑郁的神经胶质细胞减少的基础。结果：我们发现，暴露于慢性不可预测应激(CUS)15天后，新皮质细胞增殖显著减少约35%。这种影响取决于应激的持续时间、强度和类型，并且是地区特有的。细胞表型分析显示少突胶质细胞和内皮细胞数量减少。最后，使用ACUS范式可以分析快感缺失，我们发现慢性抗抑郁药物的应用逆转了皮质细胞增殖的减少，以及蔗糖偏好的不足。结论：这些发现与细胞增殖减少可能导致抑郁受试者前额叶皮质胶质细胞减少的可能性一致，并进一步阐明了应激和抗抑郁药物的细胞作用。
Background: One of the most consistent morphologic findings in postmortem studies of brain tissue from depressed patients is a decrease in the number of glia in the prefrontal cortex. However, little is known about the mechanisms that contribute to this decrease in cell number.Methods: To address this question, we subjected adult rats to chronic stress, a vulnerability factor for depression, and measured cell proliferation as a potential cellular mechanism that could underlie glial reduction in depression.Results: We found that exposure to chronic unpredictable stress (CUS) for 15 days significantly decreased cell proliferation in neocortex by approximately 35%. This effect was dependent on the duration, intensity and type of stress, and was region-specific. Analysis of cell phenotype demonstrated that there was a decrease in the number of oligodendrocytes and endothelial cells. Finally, using aCUS paradigm that allows for analysis of anhedonia, we found that chronic antidepressant administration reversed the decrease in cortical cell proliferation, as well as the deficit in sucrose preference.Conclusion: These findings are consistent with the possibility that decreased cell proliferation could contribute to reductions in glia in prefrontal cortex of depressed subjects and further elucidate the cellular actions of stress and antidepressants.