Maternal behavior and the neonatal HPA axis in the Wistar Audiogenic Rat (WAR) strain: early life implications for a genetic animal model in epilepsy

Abstract

Epileptogenesis is a multistage process and seizure susceptibility can be influenced by stress early in life. Wistar Audiogenic Rat (WAR) strain is an interesting model to study the association between stress and epilepsy, since it is naturally susceptible to seizures and present changes in the hypothalamus-pituitary-adrenal (HPA) axis activity. All these features are related to the pathogenic mechanisms usually associated to psychiatric comorbidities present in epilepsy. Therefore, the current study aimed to evaluate the neonate HPA axis function and maternal care under control and stress conditions in the WAR strain. Maternal behavior and neonate HPA axis were evaluated in Wistar and WAR strains under rest and after the presence of stressors. We observed that WAR pups present higher plasmatic corticosterone concentration as compared to Wistar pups. Although WAR dams do not show significant altered maternal behavior at rest, there is a higher latency to recover the litter in the pup retrieval test, while some did not recover all the litter. WAR dams presented similar behaviors to Wistar dams to a female intruder and maternal care with the pups in the maternal defense test. Taken together, these findings indicate that the WAR strain could show HPA axis disruption early in life and dams present altered maternal behavior under stressful events. Those alterations make the WAR strain an interesting model to evaluate vulnerability to epilepsy and its associated neuropsychiatric comorbidities.

Impacto das crises convulsivas reflexas no sistema reprodutor de fêmeas da cepa Wistar audiogenic rats

“…Isso reforça a tese de que os WAR são mais sensíveis do que as outras cepas quando se trata da dinâmica do ciclo reprodutivo e sua relação com o estresse. Uma possível explicação para isso é o fato já demonstrado de que os WAR apresentam hiperplasia do córtex da adrenal, e embora não tenham níveis basais de corticosterona mais altos do que os controles, apresentam elevações muito maiores quando expostos a uma mesma dose hormônio adrenocorticotrófico (ACTH), indicando uma resposta exacerbada do eixo HPA diante de eventos agudos de estresse (Umeoka et al, 2011, Godoy & Garcia-Cairasco, 2021.…”