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Abstract <p>The aim of this study was to evaluate the characteristicsof glucocorticoid receptor (GR) expression in Krushinsky–Molodkina(KM) rats susceptible to audiogenic seizures. GRs mediate negativefeedback in the hypothalamic–pituitary–adrenocortical axis (HPAaxis), ensuring the termination of the stress response; however,their prolonged activation may contribute to pathological plasticityof limbic system structures. We hypothesized that a defect in GR expressionor function underlies the phenotype of KM rats. In intact KM rats,compared to Wistar rats, restraint stress induced a more pronouncedand prolonged increase in corticosterone with no difference in adrenocorticotropichormone levels, indicating impaired GR-dependent inhibition of theHPA axis. In the parvocellular region of the hypothalamic paraventricularnucleus, fewer cells with GR-immunoreactive nuclei were found inKM rats. In the hippocampus, we detected no differences in <i>Nr3c1</i> gene mRNA levels or GR content.Thus, KM rats exhibit a deficit in GR-mediated regulation in thekey center of the HPA axis, but not in the hippocampus. The presentstudy established that repeated seizure stimulation (24&#xa0;episodes)also did not alter <i>Nr3c1</i> mRNA levelsin the hippocampus but led to an increase in GR protein levels inthis structure. This indicates an increased sensitivity of the hippocampusto corticosteroids in the setting of chronically elevated glucocorticoidsduring recurrent seizures, which may contribute to the mechanismsof hippocampal recruitment into the epileptic network during the developmentof audiogenic kindling.</p>

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Characteristics of Glucocorticoid Receptor Expression in the Hypothalamus and Hippocampus of Krushinsky–Molodkina Rats

  • 期刊论文

  • 发表日期：

    2026年4月19日

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  • E. L. Harbachova,
  • E. V. Chernigovskaya,
  • S. D. Nikolaeva,
  • A. A. Kulikov,
  • V. T. Bakhteeva,
  • L. S. Nikitina

摘要

Abstract

The aim of this study was to evaluate the characteristicsof glucocorticoid receptor (GR) expression in Krushinsky–Molodkina(KM) rats susceptible to audiogenic seizures. GRs mediate negativefeedback in the hypothalamic–pituitary–adrenocortical axis (HPAaxis), ensuring the termination of the stress response; however,their prolonged activation may contribute to pathological plasticityof limbic system structures. We hypothesized that a defect in GR expressionor function underlies the phenotype of KM rats. In intact KM rats,compared to Wistar rats, restraint stress induced a more pronouncedand prolonged increase in corticosterone with no difference in adrenocorticotropichormone levels, indicating impaired GR-dependent inhibition of theHPA axis. In the parvocellular region of the hypothalamic paraventricularnucleus, fewer cells with GR-immunoreactive nuclei were found inKM 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 thekey center of the HPA axis, but not in the hippocampus. The presentstudy established that repeated seizure stimulation (24 episodes)also did not alter Nr3c1 mRNA levelsin the hippocampus but led to an increase in GR protein levels inthis structure. This indicates an increased sensitivity of the hippocampusto corticosteroids in the setting of chronically elevated glucocorticoidsduring recurrent seizures, which may contribute to the mechanismsof hippocampal recruitment into the epileptic network during the developmentof audiogenic kindling.