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Abstract <p>Epilepsy and stress are strongly interrelated: while epilepsycontributes to chronic stress, the latter often triggers epilepticseizures. Temporal lobe epilepsy is frequently associated with hormonalimbalance, particularly, with dysfunction of the hypothalamic–pituitary–adrenal(HPA) axis that governs stress responses. Hormonal alterations canmodulate disease severity by affecting the functional activity of brainregions involved in epileptogenesis. We investigated the mechanismsregulating the central component of the HPA axis in a rat modelof temporal lobe epilepsy-like states induced by audiogenic kindlingin Krushinsky–Molodkina rats. Daily audiogenic stimulation was appliedfor 24&#xa0;days. Tissue samples from the hypothalamus and anterior pituitarywere collected 24 h post-seizure to assess kindling-induced long-termmolecular alterations in CRH neurons of the hypothalamic paraventricular nucleus(PVN) and corticotrophs of the anterior pituitary. No alterationswere observed in CRH production, glucocorticoid receptor expression,as well as GABAergic and glutamatergic innervation density, withinthe PVN, indicating the resilience of the HPA axis central componentto audiogenic kindling. In contrast, reduced levels of the GABAAreceptor gamma and delta subunits in the PVN, along with decreasedCRH and glutamate decarboxylase 67 (GAD67) content in the externallayer of the median eminence, indicate diminished GABAergic control ofPVN neurons and a suppression of CRH release into the portal circulation.A low CRH drive to the pituitary results in reduced CREB-mediatedsynthesis of adrenocorticotropic hormone (ACTH) in the anteriorpituitary. Thus, the elevated corticosterone secretion into thebloodstream, reported in our earlier work, is likely due to increasedsensitivity of adrenal cortical cells to ACTH, rather than to enhancedactivity of the HPA axis central component.</p>

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Effect of Audiogenic Kindling on the Central Component of Hypothalamic–Pituitary–Adrenal Axis in Krushinsky–Molodkina Rats

  • 期刊论文

  • 发表日期：

    2026年2月26日

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

摘要

Abstract

Epilepsy and stress are strongly interrelated: while epilepsycontributes to chronic stress, the latter often triggers epilepticseizures. Temporal lobe epilepsy is frequently associated with hormonalimbalance, particularly, with dysfunction of the hypothalamic–pituitary–adrenal(HPA) axis that governs stress responses. Hormonal alterations canmodulate disease severity by affecting the functional activity of brainregions involved in epileptogenesis. We investigated the mechanismsregulating the central component of the HPA axis in a rat modelof temporal lobe epilepsy-like states induced by audiogenic kindlingin Krushinsky–Molodkina rats. Daily audiogenic stimulation was appliedfor 24 days. Tissue samples from the hypothalamus and anterior pituitarywere collected 24 h post-seizure to assess kindling-induced long-termmolecular alterations in CRH neurons of the hypothalamic paraventricular nucleus(PVN) and corticotrophs of the anterior pituitary. No alterationswere observed in CRH production, glucocorticoid receptor expression,as well as GABAergic and glutamatergic innervation density, withinthe PVN, indicating the resilience of the HPA axis central componentto audiogenic kindling. In contrast, reduced levels of the GABAAreceptor gamma and delta subunits in the PVN, along with decreasedCRH and glutamate decarboxylase 67 (GAD67) content in the externallayer of the median eminence, indicate diminished GABAergic control ofPVN neurons and a suppression of CRH release into the portal circulation.A low CRH drive to the pituitary results in reduced CREB-mediatedsynthesis of adrenocorticotropic hormone (ACTH) in the anteriorpituitary. Thus, the elevated corticosterone secretion into thebloodstream, reported in our earlier work, is likely due to increasedsensitivity of adrenal cortical cells to ACTH, rather than to enhancedactivity of the HPA axis central component.