Vasopressinergic hypothalamic neurons are recruited during the audiogenic seizure of WARs

Abstract

The Wistar Audiogenic Rat (WAR) is a genetic model of reflex epilepsy with seizures induced by high-intensity sound stimulation (120 dB SPL). In spite of the known neural substrates involved in WAR seizure phenotype, neuroendocrine hypothalamic neurons were never investigated. In this work, AVP immunohistochemistry in the hypothalamus and radioimmunoassay (RIA) in plasma and in hypothalamic and hypophysial tissues were performed on both controls and WARs in order to evaluate the dynamics of AVP release due to seizure induction. Susceptible animals (WARs) displayed at least tonic–clonic convulsions followed by clonic spasms, while resistant Wistar rats (R) had no convulsive behavior. Animals were sacrificed at 3 instances: basal condition (without stimulus) and at 3 and 10 min after sound stimulation. For the immunohistochemistry AVP study, brains were harvested and processed by the avidin–biotin–peroxidase detection method. Optic densitometry was used for quantifying AVP labeling in supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei. SON presented higher densitometry levels (% D—relative to background) for both WARs and R when compared to PVN. Nevertheless, both nuclei presented a marked decrease, referenced to basal levels, in % D for WARs at 3 min (~35%) against a discrete change for R (~90%). RIA results were significantly higher in the hypophysis of WARs when compared to R rats, at 3 min. Also, at 3 min, plasma AVP in WARs (89.32 ± 24.81 pg/mL) were higher than in R (12.01 ± 2.39 pg/mL). We conclude, based on the AVP releasing profiles, that vasopressinergic hypothalamic neurons are recruited during the audiogenic seizure of WARs.