Dynamic Changes of Behavioral Despair, HPA Axis Activity, and Hippocampal Neurogenesis in Male Rats Induced by Social Defeat Stress.
Dynamic Changes of Behavioral Despair, HPA Axis Activity, and Hippocampal Neurogenesis in Male Rats Induced by Social Defeat Stress.
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DOI：
10.31083/j.jin2202043
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发表时间：
2023-02
影响因子：
1.8
通讯作者：
Hiroyoshi Harada;Masayoshi Mori;Yusuke Murata;Shunsuke Kawanabe;K. Terada;Taichi Matsumoto;K. Ohe;M. Enjoji
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文献类型：
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作者：
Hiroyoshi Harada;Masayoshi Mori;Yusuke Murata;Shunsuke Kawanabe;K. Terada;Taichi Matsumoto;K. Ohe;M. Enjoji
背景：心理社会应激因素，如威胁和失败，是抑郁症发生的主要危险因素。由于大脑中的应激反应是以应激频率相关的方式变化的，因此应激诱导抑郁的确切机制尚不清楚。目前对抑郁症发病机制的研究主要集中在抑郁样行为表型、下丘脑-垂体-肾上腺(HPA)轴和海马神经发生上。然而，大多数研究都评估了在暴露于心理社会压力后的特定时间点抑郁症的症状特征。在这里，我们研究了心理社会压力对大鼠抑郁相关特征的频率依赖性影响。方法采用常驻/入侵者实验范式，对19只雄性SD大鼠施加不同频率(1次、2次、3次或4次)的心理社会应激。随后，对大鼠进行应激反应测试，以评估HPA轴的活性，然后进行强迫游泳实验(FST)中的不动行为评估和成年神经发生。结果一次性应激大鼠FST内不动行为减少，双皮质激素(DCX)阳性细胞数量减少。二次应激可引起HPA轴活动减退。相反，4次应激后大鼠的不动行为和HPA轴活性增加，但DCX阳性细胞数量减少。结论心理社会应激对抑郁症状的影响具有应激频率依赖性的双相效应，为进一步研究抑郁症的发病机制提供了新的思路。
BACKGROUND Psychosocial stress factors, such as threat and defeat, are major risk factors for the development of depression. The precise mechanisms underlying stress-induced depression are not clearly understood because the stress response in the brain varies in a stress-frequency-dependent manner. In the current research milieu on the pathogenesis of depression, the focus is on depression-like behavioral phenotype, hypothalamic-pituitary-adrenal (HPA) axis, and hippocampal neurogenesis. However, most studies have evaluated the symptomatic features of depression at certain time points after exposure to psychosocial stress. Here, we examined the frequency-dependent effects of psychosocial stress on depression-related features in rats. METHODS In the present study, different frequencies (one, two, three, or four times) of psychosocial stress were applied to 19 male Sprague-Dawley rats using a resident/intruder paradigm. Subsequently, the rats were subjected to a stress reactivity test to evaluate HPA axis activity, following which assessments of immobility behavior in the forced swimming test (FST) and adult neurogenesis were conducted. RESULTS One-time stressed rats showed a decrease in immobility behavior in the FST and the amount of doublecortin (DCX)-positive cells. Two-time stress caused hypoactivity of the HPA axis. In contrast, immobility behavior and HPA axis activity were increased after four-time stress exposure, but the number of DCX-positive cells was decreased. CONCLUSIONS Our findings suggest that psychosocial stress produces a biphasic effect on the symptoms of depression in a stress-frequency-dependent manner, which could provide insights to facilitate further pathogenesis research on depression.