Adolescent bisphenol-A exposure decreases dendritic spine density: role of sex and age.

Adolescent bisphenol-A exposure decreases dendritic spine density: role of sex and age.
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DOI:
10.1002/syn.21758
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发表时间:
2014-11
期刊:
Synapse (New York, N.Y.)
影响因子:
--
通讯作者:
Frankfurt M
Frankfurt M
中科院分区:
其他
文献类型:
--
作者:
Bowman RE;Luine V;Khandaker H;Villafane JJ;Frankfurt M

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双酚A(BPA)是一种常见的环境内分泌干扰物,在整个生命周期中调节雌激素、雄激素和抗雄激素作用。我们最近发现,青春期接触低剂量BPA会增加焦虑,并损害空间记忆,与性别无关。在本研究中,6周龄的Sprague道利大鼠(n=24只雄性,n=24只雌性)每天接受BPA或溶媒皮下注射(40 μg/kg体重),持续一周。在7岁(队列1)和11(队列2)周的血清皮质酮水平在1小时的约束压力和脊柱密度进行了检查。青少年BPA暴露并没有改变应激依赖的皮质酮反应,但减少棘密度的锥体细胞的顶部和基底树突内侧前额叶皮层(mPFC)和海马CA 1区(CA 1)。在mPFC和CA 1的基底树突上观察到棘密度的性别差异,女性的棘密度大于男性。这种性别差异进一步扩大了年龄和治疗,结果表明,BPA依赖性的减少棘密度在男性比女性更明显的mPFC基底树突。重要的是,在暴露于低于当前U.S.E.P.A.的BPA水平的动物中观察到了强烈的神经元变化。安全的每日限额。这些结果首次表明,青春期给予BPA会对成年期的神经形态产生持久影响。鉴于人类通常通过各种来源暴露于低水平的BPA,BPA暴露后雄性和雌性大鼠报告的脊柱密度降低值得进一步研究。
Bisphenol-A (BPA), a common environmental endocrine disruptor, modulates estrogenic, androgenic, and anti-androgenic effects throughout the lifespan. We recently showed that low dose BPA exposure during adolescence increases anxiety and impairs spatial memory independent of sex. In the current study, six week old Sprague Dawley rats (n=24 males, n=24 females) received daily subcutaneous injections (40 μg/kg bodyweight) of BPA or vehicle for one week. Serum corticosterone levels in response to a 1 h restraint stress and spine density were examined at age 7 (cohort 1) and 11 (cohort 2) weeks. Adolescent BPA exposure did not alter stress dependent corticosterone responses but decreased spine density on apical and basal dendrites of pyramidal cells in the medial prefrontal cortex (mPFC) and hippocampal CA1 region (CA1). Sex differences in spine density were observed on basal dendrites of the mPFC and CA1 with females having greater spine density than males. This sex difference was further augmented by both age and treatment, with results indicating that BPA-dependent decreases in spine density were more pronounced in males than females on mPFC basal dendrites. Importantly, the robust neuronal alterations were observed in animals exposed to BPA levels below the current U.S.E.P.A. recommended safe daily limit. These results are the first demonstrating that BPA given during adolescence leads to enduring effects on neural morphology at adulthood. Given that humans are routinely exposed to low levels of BPA through a variety of sources, the decreased spine density reported in both male and female rats after BPA exposure warrants further investigation.
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