Short- and long-term effects of intermittent social defeat stress on brain-derived neurotrophic factor expression in mesocorticolimbic brain regions.
Short- and long-term effects of intermittent social defeat stress on brain-derived neurotrophic factor expression in mesocorticolimbic brain regions.
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DOI：
10.1016/j.neuroscience.2010.02.064
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发表时间：
2010-05-19
期刊：
影响因子：
3.3
通讯作者：
Nikulina, E. M.
中科院分区：
文献类型：
--
作者：
Fanous, S.;Hammer, R. P., Jr.;Nikulina, E. M.
社交失败压力是一种行为学上显着的压力源，它会激活多巴胺能区域，并且当反复经历时，会对多巴胺能功能和相关行为产生长期影响。这些长期后果的机制仍不清楚。介导这些效应的一个潜在候选者是脑源性神经营养因子（BDNF），这是一种参与突触可塑性的神经营养蛋白，并在多巴胺能区域响应各种类型的压力而发生变化。在这项研究中，我们试图确定重复的社交失败压力是否会在最后一次压力暴露后立即或四个星期后改变多巴胺能大脑区域的 BDNF mRNA 和蛋白质表达。雄性Sprague-Dawley大鼠承受社会挫败压力，包括每三天与一只好斗的雄性大鼠短暂对抗，持续10天；对照大鼠按照相同的时间表进行处理。最后一次应激或处理事件后 2 小时或 28 天对动物实施安乐死。我们的结果表明，应激后 2 小时，内侧前额叶皮质中的 BDNF 蛋白和 mRNA 表达增加。此时，杏仁核中的 BDNF mRNA 增加，黑质中的蛋白质表达增加。应激后 28 天，内侧杏仁核和腹侧被盖区 BDNF 蛋白和 mRNA 表达升高。鉴于 BDNF 在神经可塑性中的作用，持久的 BDNF 改变可能对于神经适应社会压力具有重要意义。因此，多巴胺能大脑区域响应重复社会压力的 BDNF 表达的动态性质可能对与多巴胺能功能相关的持久神经化学和行为变化产生影响。
Social defeat stress is an ethologically salient stressor which activates dopaminergic areas and, when experienced repeatedly, has long-term effects on dopaminergic function and related behavior. The mechanism for these long-lasting consequences remains unclear. A potential candidate for mediating these effects is brain-derived neurotrophic factor (BDNF), a neurotrophin involved in synaptic plasticity and displaying alterations in dopaminergic regions in response to various types of stress. In this study, we sought to determine whether repeated social defeat stress altered BDNF mRNA and protein expression in dopaminergic brain regions either immediately after the last stress exposure or four weeks later. Male Sprague-Dawley rats were subjected to social defeat stress consisting of brief confrontation with an aggressive male rat every third day for 10 days; control rats were handled according to the same schedule. Animals were euthanized either 2 h or 28 days after the last stress or handling episode. Our results show that 2 h after stress, BDNF protein and mRNA expression increased in the medial prefrontal cortex. At this time-point, BDNF mRNA increased in the amygdala and protein expression increased in the substantia nigra. Twenty-eight days after stress, BDNF protein and mRNA expression were elevated in the medial amygdala and ventral tegmental area. Given the role of BDNF in neural plasticity, BDNF alterations that are long-lasting may be significant for neural adaptations to social stress. The dynamic nature of BDNF expression in dopaminergic brain regions in response to repeated social stress may therefore have implications for lasting neurochemical and behavioral changes related to dopaminergic function.
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