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<p>Aging is associated with chronic low-grade inflammation in the hypothalamus, hyperactivation of the hypothalamic–pituitary–adrenal (HPA) axis, and disruption of circadian rhythms of glucocorticoid secretion. Using the immunoblotting method, we found that a course of ethylmethylhydroxypyridine succinate (100 mg/kg, daily intraperitoneal injections for 14 days) reduced the level of inflammatory cytokines (IL-1β, TNFα) in the hypothalamus of aged (18-month-old) rats and upregulated the expression of anti-inflammatory cytokines (TGF-β1 and IL-10), growth factors (VEGF and BDNF), markers of mitochondriogenesis (PGC-1α, NDUFV2, SDHA, cyt c1, and COX2) and synaptogenesis (SYP), succinate receptor SUCNR1, and insulin receptor INSRβ. These molecular changes were associated with reduced circulating corticosterone levels, as determined by ELISA. Our findings demonstrate the normalizing effect of succinate/SUCNR1 signaling on the circadian activity of the HPA axis during aging.</p>

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Ethylmethylhydroxypyridine Succinate Limits Inflammatory-Degenerative Changes in the Hypothalamus and Corrects Disturbances in the Circadian Rhythm of Corticosterone Secretion in Aged Rats

  • 期刊论文

  • 发表日期：

    2026年6月2日

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  • Y. I. Kirova,
  • O. L. Terekhina

摘要

Aging is associated with chronic low-grade inflammation in the hypothalamus, hyperactivation of the hypothalamic–pituitary–adrenal (HPA) axis, and disruption of circadian rhythms of glucocorticoid secretion. Using the immunoblotting method, we found that a course of ethylmethylhydroxypyridine succinate (100 mg/kg, daily intraperitoneal injections for 14 days) reduced the level of inflammatory cytokines (IL-1β, TNFα) in the hypothalamus of aged (18-month-old) rats and upregulated the expression of anti-inflammatory cytokines (TGF-β1 and IL-10), growth factors (VEGF and BDNF), markers of mitochondriogenesis (PGC-1α, NDUFV2, SDHA, cyt c1, and COX2) and synaptogenesis (SYP), succinate receptor SUCNR1, and insulin receptor INSRβ. These molecular changes were associated with reduced circulating corticosterone levels, as determined by ELISA. Our findings demonstrate the normalizing effect of succinate/SUCNR1 signaling on the circadian activity of the HPA axis during aging.