Mechanisms of Regulation of Vasopressinergic Neurons in the Hypothalamus of Rats Predisposed to Audiogenic Epilepsy

Abstract

We report here studies of the role of the ERK1/2 signal cascade in regulating the activity of vasopressinergic neurons in the hippocampus in intact Krushinskii–Molodkina (KM) rats and during and after convulsive seizures. No differences were seen in phospho-ERK1/2 kinase or phospho-CREB contents in the supraoptic nucleus (SON) of the hypothalamus between intact KM and Wistar rats. There were no differences in vasopressin RNA contents or decreases in vasopressin-neurophysin II contents in hypothalamic neurons between KM rats and Wistar rats. We have previously demonstrated reduced levels of vasopressin secretion into the blood in intact KM rats [1]. The present data indicate that impairments in the activity of the hypothalamo-hypophyseal system in KM rats mainly affect the mechanisms of neurohormone secretion, without affecting the ERK1/2- and or CREB-dependent pathways regulating vasopressin expression in SON neurons. Audiogenic convulsive seizures in KM rats led to decreases in the number of phospho-CREB-immunopositive nuclei in the SON at the clonic-tonic stage. The number of phospho-ERK1/2-immunopositive cells was no different from that in controls. At 1 h after convulsions, the numbers of phospho-ERK1/2- and phospho-CREB-immunopositive nuclei in the SON increased from those at the clonic-tonic stage of convulsions. Activation of ERK1/2/CREB-dependent intracellular signaling and increases in the expression of c-Fos protein were accompanied by increases in vasopressin transcription and increases in the neurophysin II content in SON neurons. At 24 h post-seizure, the activity of the ERK1/2 signal cascade decreased to the control level, which led to a decrease in the level of vasopressin transcripts, also to the control level. Thus, restoration of the state of the vasopressinergic system (compensatory resynthesis) 1 h after audiogenic seizures was mediated by the ERK1/2/CREB-dependent pathway.