Effects Of Early Exposure To Bisphenol A On Hippocampal Oligodendrocytes And Fear Learning In Male Adult Rats

Lactational period is a pivotal window for the development of rat brain. Accumulating evidence has demonstrated that the rats subject to continuous exposure to bisphenol A(BPA) within this period exhibit abnormal brain development and behaviors upon spanning into adulthood. Our previous studies have also shown that rats experiencing perinatal/postnatal exposure to BPA at levels approximating that in natural environment display aberrant development and function of brain, as manifested by hyperactivity and impaired spatial learning and memory. While many studies reveal that the effect of BPA on brain is mainly through disrupting neuronal development and function, little is known whether, and if yes, how BPA affects glia cells. Recent studies have demonstrated that estradiol is capable of regulating the differentiation, maturation and apoptosis of oligodendrocyte, raising a possibility that the disruption of estrogen signaling following BPA exposure may also alter the development and function of oligodendrocytes. To test this, we exposed the rats to low level of BPA from their birth until weaning and investigated whether such a treatment would affect hippocampus-dependent contextual fear learning in rats when they enter into their adulthood. We also examined the effect of lactational BPA exposure on the density of oligodendrocytes and MBP expression level in the hippocampus of adult rats, followed by analyzing the potential relationship between the expression of MBP and the level of contextual fear learning in individual rats. Our results showed that lactational BPA exposure impaired contextual fear learning in adulthood; it not only reduced the density of oligodendrocytes but also down-regulated MBP expression in adult hippocampus. Furthermore, there was a significant causal relationship between the altered MBP expression and impaired contextual fear learning in rats exposed to BPA. Altogether, our findings suggest that the altered oligodendrocytes development and function in hippocampus may be a likely explanation for the impaired contextual fear learning in adult rats experiencing lactational BPA exposure. Further efforts are needed to reveal how BPA interferes with the development and function of oligodendrocytes with subsequent alteration of hippocampus function.