Is adolescence a sensitive period for depression? Behavioral and neuroanatomical findings from a social stress model
Is adolescence a sensitive period for depression? Behavioral and neuroanatomical findings from a social stress model
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DOI：
10.1002/syn.20462
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发表时间：
2008-01-01
期刊：
影响因子：
2.3
通讯作者：
Andersen, Susan L.
中科院分区：
文献类型：
--
作者：
Leussis, Melanie P.;Andersen, Susan L.
目的：青春期期间抑郁症状出现性别差异，女性比男性面临更高的风险。然而，发育过程中的不良生活事件对男性的影响更大。需要一种结合青春期压力后行为和解剖学变化的动物模型。实验设计：Sprague-Dawley 大鼠暴露于社会压力（SS；P30-35 期间的隔离饲养）或保持群养（GRP），并在强迫游泳测试（FST）、三元习得性无助模型（LH）和高架十字迷宫中进行测试。髓磷脂碱性蛋白 (MBP) 和突触素 (SVP) 以及脊髓蛋白的蛋白质免疫印迹分别指示突触和树突可塑性。主要观察结果：在 P36，SS 增加了两性的攀爬行为，并减少了雌性在 FST 中 15 分钟不可避免的游泳后的静止潜伏期。 24小时后，两性的抑郁样行为均有不同程度的升高。在 FST 和 LH 范式中，GRP 女性比 GRP 男性表现出更高水平的抑郁相关行为。 SS 显着增加了男性 FST 中的抑郁行为，并损害了他们逃避先前可控的休克的能力。 SS 仅减少雌性的张臂时间。在前额皮质中观察到突触可塑性蛋白的最大减少：脊髓蛋白（19.1%）、SVP（7.9%）和MBP（48.7%，仅限男性）。在海马和杏仁核中观察到脊髓蛋白的较小程度的减少。结论：青少年分离会产生与压力相关的抑郁和焦虑相关的行为和神经变化。需要做更多的工作来提高我们对压力的理解，因为压力与这个脆弱的发展时期的抑郁症有关。
Objectives: Sex differences in depressive symptoms emerge during adolescence, with females more at risk than males. However, adverse life events during development have greater impact on males. An animal model that incorporates behavioral and anatomical changes following adolescent stress is needed. Experimental Design: Sprague-Dawley rats were exposed to social stress (SS; isolation housing during P30-35) or remained group-housed (GRP) and tested in the forced swim test (FST), the triadic learned helplessness model (LH), and the elevated plus maze. Western immunoblots of myelin basic protein (MBP) and synaptophysin (SVP) and spinophillin indexed synaptic and dendritic plasticity, respectively. Principal Observations: At P36, SS increased climbing behavior in both sexes, and decreased the latency to immobility in females following a 15 min inescapable swim in the FST. Depressive-like behaviors were differentially elevated in both sexes 24 h later. GRP females exhibited higher levels of depression-related behaviors than GRP males in both FST and LH paradigms. SS significantly increased depressive behaviors in the FST in males, and impaired their ability to escape shock previously conditioned to be controllable. SS decreased open arm time in females only. The greatest reductions in synaptic plasticity proteins were observed in the prefrontal cortex: spinophillin (19.1%), SVP (7.9%), and MBP (48.7%, males only). Smaller reductions in spinophillin were observed in the hippocampus and amygdala. Conclusions: Adolescent separation produces both behavioral and neural changes associated with stress-related depression and anxiety. Additional work is needed to improve our understanding of stress as it relates to depression during this vulnerable period of development.