Hippocampal AMPA receptors mediate the impairment of spatial learning and memory in prenatally stressed offspring rats

Abstract

Numerous studies have shown that prenatal stress (PS) induces learning and memory deficits in offspring, yet the specific mechanisms and effective interventions remain limited. Chewing has been known as one of the active coping strategies to suppress stress, but its effects during PS on learning and memory are unknown. The purpose of this study was to investigate the role of hippocampal AMPA receptors in the adverse effects of PS on spatial learning and memory, and whether chewing during PS could prevent these effects in prenatally stressed adult offspring rats. Prenatal restraint stress with or without chewing to dams during the day 11-20 of pregnancy was used to analyze the impact of different treatments for offspring. The spatial learning and memory were tested by the Morris water maze. The mRNA and protein expression of AMPA receptors in the hippocampus were measured by qRT-PCR and Western blot, respectively. The methylation of AMPA receptors was detected by bisulfite sequencing PCR. Our results revealed that PS impaired spatial learning acquisition and memory retrieval in adult offspring rats, but chewing could relieve this effect. Hippocampal GluA1-4 expression was significantly reduced in prenatally stressed offspring, while there were no changes in the methylation level of GluA2 and GluA4 promoters. Moreover, chewing increased PS-induced suppression of AMPA receptors in the hippocampus. In short, hippocampal AMPA receptors mediate the impairment of spatial learning and memory in prenatally stressed offspring, whereas chewing during PS could ameliorate PS-induced memory deficits.

Keywords: AMPA receptors; Chewing; Prenatal stress; Spatial learning and memory.