Effects of estradiol on learned helplessness and associated remodeling of hippocampal spine synapses in female rats.
Effects of estradiol on learned helplessness and associated remodeling of hippocampal spine synapses in female rats.
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DOI：
10.1016/j.biopsych.2009.08.017
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发表时间：
2010-01-15
影响因子：
10.6
通讯作者：
Duman, Ronald S.
中科院分区：
文献类型：
--
作者：
Hajszan, Tibor;Szigeti-Buck, Klara;Sallam, Nermin L.;Bober, Jeremy;Parducz, Arpad;MacLusky, Neil J.;Leranth, Csaba;Duman, Ronald S.
尽管女性患抑郁症的可能性是男性的两倍，但我们对女性抑郁症神经生物学的了解是有限的。我们最近在雄性大鼠身上报道，无助行为的发展与海马棘突触的严重丧失有关，这一点可以通过抗抑郁剂地塞帕明的治疗而逆转。考虑到雌二醇具有与抗抑郁药相似的海马区突触生成作用，雌二醇在女性生殖过程中的存在可能会影响对应激和抑郁的行为和突触反应。应用电子显微镜体视学方法，对去卵巢雌性大鼠(n=70)在不同雌二醇暴露条件下的海马棘突触与无助行为的关系进行了分析。应激导致海马棘突触的急性和持续性丢失，而地塞帕明的亚慢性治疗逆转了应激诱导的突触丢失。无论是在应激前还是在非应激动物逃避测试之前给予雌激素补充，都会增加海马棘突触的数量。相关分析表明，无助行为的严重程度与海马棘突触数目呈显著负相关。这些发现表明，海马棘突触重塑可能是导致获得性无助的关键因素，也可能是抑郁症的神经生物学因素。
Despite the fact that women are twice as likely to develop depression as men, our understanding of depression neurobiology in females is limited. We have recently reported in male rats that development of helpless behavior is associated with a severe loss of hippocampal spine synapses, which is reversed by treatment with the antidepressant, desipramine. Considering the fact that estradiol has a hippocampal synaptogenic effect similar to those of antidepressants, the presence of estradiol during the female reproductive life may influence behavioral and synaptic responses to stress and depression. Using electron microscopic stereology, we analyzed hippocampal spine synapses in association with helpless behavior in ovariectomized female rats (n=70), under different conditions of estradiol exposure. Stress induced an acute and persistent loss of hippocampal spine synapses, while subchronic treatment with desipramine reversed the stress-induced synaptic loss. Estradiol supplementation given either prior to stress or prior to escape testing of nonstressed animals both increased the number of hippocampal spine synapses. Correlation analysis demonstrated a statistically significant negative correlation between the severity of helpless behavior and hippocampal spine synapse numbers. These findings suggest that hippocampal spine synapse remodeling may be a critical factor underlying learned helplessness and, possibly, the neurobiology of depression.
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影响因子：
10.6
作者：
Autry, Anita E.;Adachi, Megumi;Cheng, Pengfei;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
影响因子：
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作者：
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影响因子：
10.6
作者：
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Duman, RS
影响因子：
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作者：
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影响因子：
4.1
作者：
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通讯作者：
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