Long-term effects of adolescent exposure to bisphenol A on neuron and glia number in the rat prefrontal cortex: Differences between the sexes and cell type

Abstract

Bisphenol A (BPA), an endocrine disruptor used in a variety of consumer products, has been found to alter the number of neurons in multiple brain areas in rats following exposure in perinatal development. Both the number of neurons and glia also change in the medial prefrontal cortex (mPFC) during adolescence, and this process is known to be influenced by gonadal hormones which could be altered by BPA. In the current study, we examined Long-Evans male and female rats that were administered BPA (0, 4, 40, or 400 µg/kg/day) during adolescent development (postnatal days 27–46). In adulthood (postnatal day 150), the number of neurons and glia in the mPFC were stereologically assessed in methylene blue/azure II stained sections. There were no changes in the number of neurons, but there was a significant dose by sex interaction in number of glia in the mPFC. Pairwise comparisons between controls and each dose showed a significant increase in the number of glia between 0 and 40 µg/kg/day in females, and a significant decrease in the number of glia between 0 and 4 µg/kg/day in males. In order to determine the type of glial cells that were changing in these groups in response to adolescent BPA administration, adjacent sections were labelled with S100β (astrocytes) and IBA-1 (microglia) in the mPFC of the groups that differed. The number of microglia was significantly higher in females exposed to 40 µg/kg/day than controls and lower in males exposed to 4 µg/kg/day than controls. There were no significant effects of adolescent exposure to BPA on the number of astrocytes in male or females. Thus, adolescent exposure to BPA produced long-term alterations in the number of microglia in the mPFC of rats, the functional implications of which need to be explored.

Analysis of c-Fos induction in response to social interaction in male and female Fisher 344 rats

“…Although there are sex differences in the timing of neuronal loss (Willing and Juraska, 2015) and dendritic complexity (Markham et al, 2013) in adolescence, less is known about sex differences in neuron number in adulthood that could contribute to the changes observed in the PFC. Previous studies have reported no sex differences in the number of neurons in the mPFC in adult Long Evans rats (Koss et al, 2012; Wise et al, 2016). In addition, Sprague Dawley females (P62) exhibit fewer and shorter branches in apical, but not basilar, dendrites in the mPFC, compared to their male counterparts (Garrett and Wellman, 2009).…”

Perinatal BPA exposure alters body weight and composition in a dose specific and sex specific manner: The addition of peripubertal exposure exacerbates adverse effects in female mice

“…Therefore, we do not know whether peripubertal exposure alone would cause the changes observed in the P + P females or whether they may result from a more prolonged exposure to BPA. Peripubertal exposure has been reported to alter microglia number in the prefrontal cortex in female rats [61] and to increase ER alpha levels in several brain nuclei in female but not male mice [62] and rats [63]. As mentioned previously, male and female C57BL/6J mice exposed to BPA solely during the mid through post adolescent period revealed marked increases in body weight and adiposity at the end of the exposure period [50] suggesting that this period could be a critical window for the obesogenic properties of BPA.…”

Developmental neurotoxicants and the vulnerable male brain: a systematic review of suspected neurotoxicants that disproportionally affect males

“…Both BPA and phthalates are endocrine disruptors at low levels (Wise et al 2016). Because of their widespread use, exposures are of concern.…”

“…BPA has been shown to alter the sex-specific colonization of the hippocampus and amygdala by microglia (Rebuli et al 2016). However, in regard to which gender may be more vulnerable to the neurotoxic effects of BPA, the evidence appears to be somewhat mixed (Wise et al 2016). …”