Pizarro José M, Lumley Lucille A, Medina Wilma, Robison Christopher L, Chang Wenling E, Alagappan Arun, Bah Mariama J, Dawood Mustansir Y, Shah Jinesh D, Mark Brian, Kendall Nadia, Smith Mark A, Saviolakis George A, Meyerhoff James L
Division of Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, USA.
Brain Res. 2004 Oct 29;1025(1-2):10-20. doi: 10.1016/j.brainres.2004.06.085.
Acute social defeat in mice activates the hypothalamic-pituitary-adrenal axis (HPA) and induces long-term behavioral changes, including exaggerated fear responses and inhibition of territorial behavior. Stress-induced hormonal and neurotransmitter release may contribute to disruption of expression of genes important for cell survival, neuronal plasticity, and neuronal remodeling. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor associated with structural cellular changes that occur during nervous system development and contributes to neural plasticity in the adult brain. In rats, acute (1-2 h) restraint stress transiently reduces BDNF mRNA expression in the hippocampus, a region important in the memory and in HPA regulation; restraint stress also decreases BDNF expression in the basolateral amygdala (BLA), a region important for fear consolidation and emotional memory. We hypothesized that a brief (10 min) exposure to intense social stress, a more naturalistic stressor than restraint stress, would also reduce BDNF mRNA in the hippocampus and BLA of mice. In the present study, we examined the time course of expression of BDNF mRNA expression in the hippocampus and amygdala, as well as other subcortical and cortical brain regions, following acute social stress. In situ hybridization analysis for BDNF mRNA expression showed that there was a significant decrease in BDNF mRNA expression in all regions studied in mice 24 h after social defeat when compared to control (naive) mice (P<0.05). These findings support our hypothesis that BDNF mRNA levels are reduced by social stress, and may have implications for brain plasticity and behavioral changes following social stress.
小鼠急性社会挫败会激活下丘脑-垂体-肾上腺轴（HPA），并引发长期行为变化，包括过度恐惧反应和领地行为抑制。应激诱导的激素和神经递质释放可能导致对细胞存活、神经元可塑性和神经元重塑至关重要的基因表达受到破坏。脑源性神经营养因子（BDNF）是一种神经营养因子，与神经系统发育过程中发生的结构性细胞变化相关，并有助于成年大脑的神经可塑性。在大鼠中，急性（1-2小时）束缚应激会短暂降低海马体（对记忆和HPA调节很重要的区域）中的BDNF mRNA表达；束缚应激还会降低基底外侧杏仁核（对恐惧巩固和情绪记忆很重要的区域）中的BDNF表达。我们假设，短暂（10分钟）暴露于强烈社会应激（一种比束缚应激更符合自然情况的应激源）也会降低小鼠海马体和基底外侧杏仁核中的BDNF mRNA。在本研究中，我们研究了急性社会应激后，海马体、杏仁核以及其他皮质下和皮质脑区中BDNF mRNA表达的时间进程。BDNF mRNA表达的原位杂交分析表明，与对照（未经历过应激的）小鼠相比，社会挫败后24小时，小鼠所有研究区域中的BDNF mRNA表达均显著下降（P<0.05）。这些发现支持了我们的假设，即社会应激会降低BDNF mRNA水平，并且可能对社会应激后的大脑可塑性和行为变化具有影响。
