Extracellular signal-regulated kinase 2 signaling in the hippocampal dentate gyrus mediates the antidepressant effects of testosterone.
Extracellular signal-regulated kinase 2 signaling in the hippocampal dentate gyrus mediates the antidepressant effects of testosterone.
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DOI：
10.1016/j.biopsych.2011.11.028
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发表时间：
2012-04-01
影响因子：
10.6
通讯作者：
Kabbaj, Mohamed
中科院分区：
文献类型：
--
作者：
Carrier, Nicole;Kabbaj, Mohamed
人类和动物研究表明，睾酮可能具有抗抑郁作用。在这项研究中，我们试图研究海马体内睾酮抗抑郁作用的分子机制，海马是抑郁症病因的基础区域。采用蔗糖偏好试验和强迫游泳试验研究了睾酮替代对性腺去角质成年雄性大鼠的影响。我们探讨了睾酮对海马神经发生和应激相关分子基因表达的可能影响。通过使用病毒载体，我们探索了睾酮介导快感缺乏的抗抑郁分子机制，并在睾丸激素替代的性腺去角质大鼠齿状回中操纵细胞外信号调节激酶2 （ERK2）的表达。睾酮在蔗糖偏好和FSTs中具有抗抑郁作用，可能是通过对雌激素代谢物的芳香化介导的，尽管对海马细胞增殖或存活没有影响。我们发现了海马ERK2表达的睾酮依赖性调节。在功能上，在接受睾酮补充的去腺大鼠中，减少齿状回内ERK2活性可诱导快感缺乏，而在去腺大鼠中，ERK2的过表达可挽救这种行为。这些结果暗示了ERK2信号在海马齿状回区域内作为睾酮抗抑郁作用的关键中介的作用。
Human and animal studies suggest that testosterone may have antidepressant effects. In this study, we sought to investigate the molecular mechanisms underlying the antidepressant effects of testosterone within the hippocampus, an area that is fundamental in the etiology of depression. The effects of testosterone replacements in gonadectomized adult male rats were investigated using the sucrose preference and forced swim tests. We explored possible effects of testosterone on hippocampal neurogenesis and gene expression of stress-related molecules. Through the use of viral vectors we pursued the antidepressant molecular mechanism(s) of testosterone in mediating anhedonia, and manipulated extracellular signal-regulated kinase 2 (ERK2) expression in the dentate gyrus in gonadectomized rats with testosterone replacements. Testosterone had antidepressant effects, likely mediated by aromatization to estrogen metabolites, in the sucrose preference and FSTs despite having no effects on hippocampal cell proliferation or survival. We found a testosterone-dependent regulation of hippocampal ERK2 expression. Functionally, reducing ERK2 activity within the dentate gyrus induced anhedonia in gonadectomized rats receiving testosterone supplementation, while the overexpression of ERK2 rescued this behavior in gonadectomized rats. These results implicate a role for ERK2 signaling within the dentate gyrus area of the hippocampus as a key mediator of the antidepressant effects of testosterone.
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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：
11
作者：
Bessa, J. M.;Ferreira, D.;Sousa, N.
通讯作者：
Sousa, N.
DOI：
10.1037/h0077264
发表时间：
1976-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
GENTRY, RT;WADE, GN
通讯作者：
WADE, GN
影响因子：
3.7
作者：
Anacker, Christoph;Zunszain, Patricia A.;Carvalho, Livia A.;Pariante, Carmine M.
通讯作者：
Pariante, Carmine M.
影响因子：
3.2
作者：
Barha, C. K.;Lieblich, S. E.;Galea, L. A. M.
通讯作者：
Galea, L. A. M.