Testosterone decrease does not play a major role in the suppression of hippocampal cell proliferation following social defeat stress in rats

Testosterone decrease does not play a major role in the suppression of hippocampal cell proliferation following social defeat stress in rats
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DOI:
10.1016/j.physbeh.2010.08.010
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发表时间:
2010-12-02
影响因子:
2.9
通讯作者:
McEwen, Bruce S.
McEwen, Bruce S.
中科院分区:
医学3区
文献类型:
--
作者:
Buwalda, Bauke;van der Borght, Karin;McEwen, Bruce S.

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已知啮齿类动物的社交失败压力对大脑生理和行为具有强烈和持久的影响,这与某些人类压力相关的精神病理学具有相似性。本实验室的先前实验表明,社交失败压力抑制睾酮分泌,并导致睾酮能5-HT 1A受体的持久脱敏。HT 1A受体结合这些受体被假设在该脑结构中的神经发生中起重要作用。我们设计了本实验来测试社交失败是否减少大鼠海马细胞增殖和神经发生,以及睾酮补充是否可以防止这种减少。结果表明,连续5天的重复社交失败应激诱导雄性大鼠血浆睾酮水平显著下降,在应激期结束后24小时和3周抑制海马细胞增殖补充睾酮防止了社会应激诱导的血浆睾酮水平下降补充激素还减少了应激后3周对海马BrdU标记的负面影响。然而,这种效果相当弱,是由激素本身抑制增殖的倾向和未能完全恢复增殖率引起的。在应激期之前或最后一次失败后24小时增殖的齿状回细胞的增殖不受社会失败的影响因此应激诱导的海马细胞增殖的降低不太可能是由社会应激期间睾酮分泌的短暂抑制引起的(C)2010 Elsevier Inc版权所有
Stress of social defeat in rodents is known to have a strong and long-lasting effect on brain physiology and behavior which bears similarities with certain human stress related psychopathologies Previous experiments in this lab showed that social defeat stress suppresses testosterone secretion and causes a lasting desensitization of the serotonergic 5-HT1A receptors Testosterone supplementation in socially stressed tree shrews prevented a decrease in hippocampal 5-HT1A receptor binding These receptors are hypothesized to play an important role in neurogenesis in this brain structure We designed the present experiment to test if social defeat reduces hippocampal cell proliferation and neurogenesis in rats and if testosterone supplementation can prevent this reduction The results indicate that repeated social defeat stress on 5 successive days Induces a significant drop in plasma testosterone levels in male rats and suppresses hippocampal cell proliferation 24 h and 3 weeks after the end of the stress period Testosterone supplementation prevented the social stress induced drop in plasma testosterone levels The hormone supplementation also reduced the negative effect of stress on hippocampal BrdU labeling at 3 weeks post-defeat This effect was however rather weak and was caused by the tendency of the hormone in itself to suppress proliferation and the failure to fully recover the proliferation rate Survival of dentate gyrus cells that either proliferated prior to the stress period or 24 h after the last defeat was not affected by the social defeats Thus the stress-induced lowering of hippocampal cell proliferation is not likely to be caused by transient inhibition of testosterone secretion during social stress (C) 2010 Elsevier Inc All rights reserved