Prenatal bisphenol A exposure impairs the aversive and spatial memory reduces the level of NMDA receptor subunits in the hippocampus of male Sprague Dawley rats

Abstract

Memory impairment in children is an ongoing issue worldwide related to a learning disability. This neurobiological condition has been suggested to associate with bisphenol A (BPA) exposure during pregnancy. BPA is an inorganic compound used to produce polycarbonate plastics and epoxy resins. We conduct this study to investigate the effects of prenatal BPA exposure on the level of the N-methyl-D-aspartate (NMDA) receptor subunits, synaptic markers of the hippocampus and neurobehavioral outcomes in rats. The pregnant rats were given a daily dose of 5 mg/kg and 50 mg/kg of BPA with 0.5% Tween 80 orally from gestation day 2 until 21 (GD21). The level of GluN2A, GluN2B, PSD-95 and synapsin I in the hippocampus and its neurobehaviour outcomes were quantified and evaluated in the male foetus and adolescent rat. Prenatal BPA exposure reduced GluN2A, GluN2B, synapsin I and PSD-95 (Postsynaptic Density-95) in the male foetus and adolescent rat hippocampus compared to the control group. The prenatal BPA exposed rats demonstrated anxiety-related behaviour and impairment in aversive and spatial memory. The findings suggested that the impairment in neurobehavioral performance may inhibit the signalling pathway in the NMDA receptor subunits in the male foetus rat hippocampus leading to learning and memory deficits when reaching adolescence.

Neurodevelopmental Effects of Prenatal Bisphenol A Exposure on the Role of MicroRNA Regulating NMDA Receptor Subunits in the Rat Hippocampus

“…To prove that the modulation of miRNA and mRNA could affect brain function, we speci cally analyzed the memory retention ability of the rats at the adolescent level (AD35). The present result was comparable with our previous nding, where prenatal BPA exposure at 5 mg/kg/day induced anxietyrelated behavior and impaired learning and memory function 41 . The open eld test is considered to cause anxiety in animals due to social isolation and fear of the novel environment, and the outcome can be altered based on the lighting condition 42,43 .…”

“…We speculate that the outcome is also related to regulating GluN2A and GluN2B in the hippocampus. In addition, our previous report has shown that the GluN2A and GluN2B protein levels in the postsynaptic membrane were decreased in the BPA-exposed AD35 rat's hippocampus 41 . Further, this study will observe the prenatal BPA effect on the activity of the GluN2A and GluN2B at a cytoplasmic level in AD35 rat hippocampus only.…”

“…This behavior is thought to be its natural thigmotaxis to avoid predators 44 . Meanwhile, in the same condition the emotional or exploratory response of BPA-treated rats possessed an increment in the frequency of grooming and fecal boli but low in rearing activity 16,41,45,46 . Given all, the open eld test is useful for studying this early life effect on anxiety, where it can be used as a part of behavioural pro ling in different learning abilities 42 .…”

“…shown that anxiety rats from the prenatal BPA study enhanced in exploratory, which closed to the wall but avoided the center area 41 . This behavior is thought to be its natural thigmotaxis to avoid predators 44 .…”

“…A number of the studies reported that prenatal BPA exposure from low (0.004, 0.04, 0.4, 0.5 and 5 mg/kg/day) to high (50 mg/kg/day) dosages able to induce impairment in learning and memory function at the adult stage 40,41,47 . Reduced learning ability in step-down passive avoidance also can be shown in prenatal BPA exposure at 1,10, 5 and 50 mg/kg/day where the rats have di culties staying on the platform 40,41,48 . While in a human study, BPA exposure during pregnancy period showed to cause aggressive behavior syndrome, attention problems, anxiety/depression, and poor language skills 9,12,49 .…”