Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis.
Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis.
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DOI：
10.3389/fnbeh.2013.00223
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发表时间：
2013
影响因子：
3
通讯作者：
Trainor BC
中科院分区：
文献类型：
--
作者：
Greenberg GD;Laman-Maharg A;Campi KL;Voigt H;Orr VN;Schaal L;Trainor BC
抑郁症和焦虑症在女性中比男性更常见，人们对导致这种差异的神经生物学机制知之甚少。最近的数据表明，应激诱导的神经营养因子的变化通过作用于不同的大脑网络而对行为产生相反的影响。社会挫折一直是了解神经营养素作用的重要方法，但雌性大鼠和小鼠的低攻击性水平限制了这些方法的应用，主要是男性。我们研究了一夫一妻制的加州小鼠(加州小鼠)的社会失败的影响，这是一种雄性和雌性都在保卫领土的物种。我们证明，失败性应激增加了女性终纹床核(BNST)成熟脑源性神经营养因子(BDNF)的蛋白，但不增加了终纹床核(BNST)的mRNA，但男性没有。BDNF蛋白的变化仅限于BNST的前亚区，而邻近的伏核(NAC)则无变化。长期小剂量的抗抑郁药物舍曲林逆转了失败对社交退缩行为和脑源性神经营养因子的影响。然而，更高剂量的舍曲林恢复了社交撤退和BDNF水平的升高。小剂量舍曲林的急性治疗未能逆转失败的影响。将选择性酪氨酸相关激酶B受体(TrkB)拮抗剂ANA-12注入BNST前部，特别是增加了应激女性的社交互动，但对天真失败的女性的行为没有影响。这些结果表明，应激诱导的BNST前部BDNF的增加有助于在女性中观察到夸大的社交退缩表型。
Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males. We examined the effects of social defeat in monogamous California mice (Peromyscus californicus), a species in which both males and females defend territories. We demonstrate that defeat stress increases mature brain-derived neurotrophic factor (BDNF) protein but not mRNA in the bed nucleus of the stria terminalis (BNST) in females but not males. Changes in BDNF protein were limited to anterior subregions of the BNST, and there were no changes in the adjacent nucleus accumbens (NAc). The effects of defeat on social withdrawal behavior and BDNF were reversed by chronic, low doses of the antidepressant sertraline. However, higher doses of sertraline restored social withdrawal and elevated BDNF levels. Acute treatment with a low dose of sertraline failed to reverse the effects of defeat. Infusions of the selective tyrosine-related kinase B receptor (TrkB) antagonist ANA-12 into the anterior BNST specifically increased social interaction in stressed females but had no effect on behavior in females naïve to defeat. These results suggest that stress-induced increases in BDNF in the anterior BNST contribute to the exaggerated social withdrawal phenotype observed in females.
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影响因子：
3.3
作者：
Greenberg, G. D.;van Westerhuyzen, J. A.;Bales, K. L.;Trainor, B. C.
通讯作者：
Trainor, B. C.
影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
影响因子：
3.5
作者：
Davis, ES;Marler, CA
通讯作者：
Marler, CA
影响因子：
3.4
作者：
Carr, Gregory V.;Lucki, Irwin
通讯作者：
Lucki, Irwin
影响因子：
5.3
作者：
Bangasser, Debbie A.;Shors, Tracey J.
通讯作者：
Shors, Tracey J.