Xu X, Liu Y, Sadamatsu M, Tsutsumi S, Akaike M, Ushijima H, Kato N
Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
Neurosci Res. 2007 Jun;58(2):149-55. doi: 10.1016/j.neures.2007.02.011. Epub 2007 Feb 23.
Bisphenol A (BPA) has been shown to interfere with thyroid hormone receptors (THRs) and to influence the expression of THR-responsive elements in vivo and in vitro, while some studies reported hyperactivity induced by BPA treatment. In the present study, our purpose was to investigate the effect of BPA exposure on behavioral alteration and its mechanism of action, especially focusing on the thyroid hormone pathway. Significant sexual difference on behaviors was observed in perinatal BPA exposure, as manifested by hyperactivity and impaired spatial learning/memory in male pups after matured. Dams treated with 0.1mg/l BPA showed transient hypothyroidism, while male pups were found to exhibit a transient hyperthyroidism followed by hypothyroidism. Furthermore, significant up-regulated expression levels of mRNA and protein of SRC-1 in the hippocampus were observed in male pups by 0.1mg/l BPA treatment. However the expression of THRalpha/beta and RC3/neurogranin were not affected by BPA treatment. These results indicate that perinatal BPA exposure at a very low level may influence thyroid function and then consequently affects brain development, but at the same time, suggest that thyroid hormone receptor may not be a direct target of BPA action, but instead, another factor may be involved in this action.
双酚A(BPA)已被证明会干扰甲状腺激素受体(THR),并在体内和体外影响THR反应元件的表达,同时一些研究报道了BPA处理会导致多动。在本研究中,我们的目的是调查BPA暴露对行为改变的影响及其作用机制,尤其关注甲状腺激素途径。围产期暴露于BPA会导致显著的行为性别差异,表现为雄性幼崽成年后多动且空间学习/记忆受损。用0.1mg/l BPA处理的母鼠出现短暂性甲状腺功能减退,而雄性幼崽则表现为短暂性甲状腺功能亢进,随后出现甲状腺功能减退。此外,用0.1mg/l BPA处理的雄性幼崽海马中SRC-1的mRNA和蛋白表达水平显著上调。然而,THRα/β和RC3/神经颗粒素的表达不受BPA处理的影响。这些结果表明,极低水平的围产期BPA暴露可能会影响甲状腺功能,进而影响大脑发育,但同时也表明甲状腺激素受体可能不是BPA作用的直接靶点,而是可能有其他因素参与了这一作用。