The aim of this study was to evaluate the characteristics of glucocorticoid receptor (GR) expression in Krushinsky–Molodkina (KM) rats susceptible to audiogenic seizures. GRs mediate negative feedback in the hypothalamic–pituitary–adrenocortical axis (HPA axis), ensuring the termination of the stress response; however, their prolonged activation may contribute to pathological plasticity of limbic system structures. We hypothesized that a defect in GR expression or function underlies the phenotype of KM rats. In intact KM rats, compared to Wistar rats, restraint stress induced a more pronounced and prolonged increase in corticosterone with no difference in adrenocorticotropic hormone levels, indicating impaired GR-dependent inhibition of the HPA axis. In the parvocellular region of the hypothalamic paraventricular nucleus, fewer cells with GR-immunoreactive nuclei were found in KM rats. In the hippocampus, we detected no differences in Nr3c1 gene mRNA levels or GR content. Thus, KM rats exhibit a deficit in GR-mediated regulation in the key center of the HPA axis, but not in the hippocampus. The present study established that repeated seizure stimulation (24 episodes) also did not alter Nr3c1 mRNA levels in the hippocampus but led to an increase in GR protein levels in this structure. This indicates an increased sensitivity of the hippocampus to corticosteroids in the setting of chronically elevated glucocorticoids during recurrent seizures, which may contribute to the mechanisms of hippocampal recruitment into the epileptic network during the development of audiogenic kindling.
Harbachova et al. (Wed,) studied this question.