Loss of Hippocampal Oligodendrocytes Contributes to the Deficit of Contextual Fear Learning in Adult Rats Experiencing Early Bisphenol A Exposure

Abstract

During early development, continuous exposure to environmental contaminants such as bisphenol A (BPA) is known to alter neuronal development, resulting in aberrant brain structure and predisposing individuals to developing neuropsychiatric disorders later in life. While the altered oligodendrocyte (OL) structure and function have been casually linked to the occurrence of numerous psychiatric diseases, it remains open whether early BPA exposure (EBE) also recruits OLs to mediate its toxicity in the brain. Here, we observed that EBE from birth to postnatal day 21 caused a substantial loss of hippocampal OLs in rat pups. The OL loss was enduring and manifested even when the affected pups spanned into their adulthood. In parallel, the expression of two key proteins in mature OLs, myelin basic protein (MBP), and monocarboxylate transporter 1 (MCT1) was markedly downregulated in adult hippocampus with a considerable reduction in the number of myelinated axons. By contrast, the myelination of individual axons remained intact. The altered hippocampal OLs were related to EBE-mediated disruption of estrogen receptor (ER) signaling in developing OLs and could be readily prevented by treatment with low level of ICI 182780, an ER antagonist. Importantly, the adult rats subject to EBE exhibited clear deficit in contextual fear memory, which highly correlated with OL loss and decreased MBP and MCT1 expression in hippocampus. The OL loss may thus represent an alternative route through which EBE has its adversity on the brain and contributes to the development of neuropsychiatric illness.

Human IPSC-Derived Model to Study Myelin Disruption

“…Following a full text review, a list of potential test chemicals was generated, containing nine substances (Figure S1). This list included cuprizone [70], toluene [71], bisphenol A (BPA) [72,73], BDE-99 [74,75], ethanol [76][77][78][79], methyl mercury [80], Tris(1,3-dichloro-2propyl) phosphate (TDCPP) [81], vanadium [82][83][84], and lead [85,86] (Figure 1G). For this study, only four chemicals were selected from this list.…”

The effects of perinatal bisphenol A exposure on thyroid hormone homeostasis and glucose metabolism in the prefrontal cortex and hippocampus of rats

“…Current evidence showed that both astrocyte–neuron and oligodendrocyte—axon lactate shuttles are important for the brain energy metabolism and support neuronal function and survival (Cater, Chandratheva, Benham, Morrison, & Sundstrom, ; Fünfschilling et al, ). Our previous work has found that early BPA exposure induced decreased expression of monocarboxylate transporter 1 (MCT1), a critical protein for transporting lactate from oligodendrocytes to myelinated axons, and more demyelinated axons in the adult hippocampus of BPA–treated rats (Xu et al, ). The decrease in lactate production (present study) and decreased MCT1 expression (previous study) in the adult hippocampus of BPA–exposed rats are likely to cause weakness of axonal energy metabolism and consequent demyelination of axons, which may be responsible for deficit of contextual fear learning in adult BPA–treated rats (Xu et al, ).…”

“…BPA is completely and rapidly absorbed from the gastrointestinal tract (Volkel, Colnot, Csanady, Filser, & Dekant, 2002). Our previous study has demonstrated that perinatal constant BPA exposure at a low dose of 0.1 mg/L via maternal drinking water, which is equivalent to about 15 μg kg -1 day -1 BPA intake (Xu et al, 2012), induced a mean BPA level of 1.7 ng/ml in serum in 21day-old pup rats which is lower than the mean value observed in girls and boys (Chen et al, 2015;Komarowska et al, 2015), and caused hyperactivity, impaired spatial memory and deficit of contextual fear learning in adulthood (Xu et al, 2014(Xu et al, , 2017. These evidences suggest that the serum BPA level in children is sufficient to lead to a spectrum of adverse consequences on brain development and behavior in rodents ranging from the hypotrophy of dendritic spine in the developing neurons to neuropsychiatric deficits (Xu et al, 2007(Xu et al, , 2013(Xu et al, , 2014.…”

How Do Cells of the Oligodendrocyte Lineage Affect Neuronal Circuits to Influence Motor Function, Memory and Mood?

“…The idea that myelination is critical for normal cognitive function is also supported by rodent preclinical models that preferentially induce oligodendrocyte loss and demyelination of the corpus callosum (Xu et al, 2010 ), hippocampus (Xu et al, 2017 ) or medial prefrontal cortex (Yang et al, 2017 ) and impair working memory. Social isolation during development, which has no effect on oligodendrocyte number, but results in thinner myelin in the prefrontal cortex and hippocampus, also impairs working memory (Makinodan et al, 2012 ; Cao et al, 2017 ).…”