Bowman Rachel E, Luine Victoria, Khandaker Hameda, Villafane Joseph J, Frankfurt Maya
Department of Psychology, Sacred Heart University, Fairfield, Connecticut, 06825.
Synapse. 2014 Nov;68(11):498-507. doi: 10.1002/syn.21758. Epub 2014 Jul 15.
Bisphenol-A (BPA), a common environmental endocrine disruptor, modulates estrogenic, androgenic, and antiandrogenic effects throughout the lifespan. We recently showed that low dose BPA exposure during adolescence increases anxiety and impairs spatial memory independent of sex. In this 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.
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，青春期低剂量接触双酚A会增加焦虑并损害空间记忆，且与性别无关。在本研究中，六周龄的斯普拉格-道利大鼠（n = 24只雄性，n = 24只雌性）连续一周每天皮下注射双酚A（40微克/千克体重）或赋形剂。在7周龄（队列1）和11周龄（队列2）时检测了对1小时束缚应激的血清皮质酮水平和树突棘密度。青春期接触双酚A并未改变应激依赖性皮质酮反应，但降低了内侧前额叶皮质（mPFC）和海马CA1区（CA1）锥体细胞顶端和基底树突上的树突棘密度。在mPFC和CA1的基底树突上观察到树突棘密度的性别差异，雌性的树突棘密度高于雄性。年龄和处理均进一步加剧了这种性别差异，结果表明，在mPFC基底树突上，双酚A依赖性的树突棘密度降低在雄性中比雌性更明显。重要的是，在接触低于美国环境保护局目前推荐的每日安全限量水平双酚A的动物中观察到了明显的神经元改变。这些结果首次表明，青春期给予双酚A会对成年期的神经形态产生持久影响。鉴于人类经常通过多种来源接触低水平的双酚A，双酚A暴露后雄性和雌性大鼠中均报告的树突棘密度降低值得进一步研究。
