Prenatal stress and early life febrile convulsions compromise hippocampal genes MeCP2/REST function in mid-adolescent life of Sprague-Dawley rats

Abstract

Early life neuronal insults exacerbate the development of febrile seizures and can result in epigenetic changes in the hippocampus. The MeCP2 and REST genes play a pivotal role in cognition as both contribute to neuronal function. In this study, cognitive function and expression of the MeCP2 and REST genes in the hippocampus were investigated in four groups of Sprague Dawley rats offspring viz. (1) Normally reared treated with saline (NSS). (2) Prenatally stressed treated with saline (SS). (3) Normally reared with febrile seizures (NSFS). (4) Prenatally stressed with febrile seizures (SFS). Pregnant dams were subjected to 1h of restraint stress for 7days starting on gestational day 14. Following birth, a once-off exposure to saline injections or febrile seizure induction was conducted on postnatal day (PND) 14. Behavioural tests were conducted using the Morris-Water maze on PND 21 and 30. Our results showed a febrile seizure effect on learning and memory in the non-stressed animals. However, febrile seizures did not exacerbate learning deficits in the prenatally stressed animals. Gene analysis found a down-regulation in MeCP2 gene expression and an up-regulation of the REST gene in prenatally stressed animals. Exposure to febrile seizure resulted in down-regulation of both MeCP2 and REST gene expression in the non-stressed animals, but febrile seizures did not exacerbate the stress effect on gene expression. This suggests that exposure to prenatal stress (SS) and febrile seizures (NSFS) may impair cognitive behavioural function. However, in the NSFS animals, there seems to be an attempt to counteract the effects of febrile seizures with time.

Keywords: Cognitive function; Epigenetics; Febrile seizures; MeCP2; Prenatal stress; REST.