ArticleInternational journal of molecular sciences2023
Interleukin 6 (IL-6) Regulates GABAA Receptors in the Dorsomedial Hypothalamus Nucleus (DMH) through Activation of the JAK/STAT Pathway to Affect Heart Rate Variability in Stressed Rats.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 5 citations in OpenAlex.
- NR3C1/PRKACG-mediated impairment of mitochondrial quality control underlies stress-induced hypothalamic neuronal injury.Communications biology · 2026Article
- Review
- HMolecular and cellular biochemistry · 2026Review
- Pathological changes in the spleen of mice subjected to different time courses of restraint stress.Scientific reports · 2024Article
- The TF/Nrf2/GSTP1 pathway is involved in stress-induced hepatocellular injury through ferroptosis.Journal of cellular and molecular medicine · 2024Article
- A diagnostic index for predicting heart rate variability decline and prognostic value in newly diagnosed non-small cell lung cancer patients.Frontiers in oncology · 2024Article
- Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery.Open medicine (Warsaw, Poland) · 2024Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The dorsomedial hypothalamus nucleus (DMH) is an important component of the autonomic nervous system and plays a critical role in regulating the sympathetic outputs of the heart. Stress alters the neuronal activity of the DMH, affecting sympathetic outputs and triggering heart rate variability. However, the specific molecular mechanisms behind stress leading to abnormal DMH neuronal activity have still not been fully elucidated. Therefore, in the present study, we successfully constructed a stressed rat model and used it to investigate the potential molecular mechanisms by which IL-6 regulates GABAA receptors in the DMH through activation of the JAK/STAT pathway and thus affects heart rate variability in rats. By detecting the c-Fos expression of neurons in the DMH and electrocardiogram (ECG) changes in rats, we clarified the relationship between abnormal DMH neuronal activity and heart rate variability in stressed rats. Then, using ELISA, immunohistochemical staining, Western blotting, RT-qPCR, and RNAscope, we further explored the correlation between the IL-6/JAK/STAT signaling pathway and GABAA receptors. The data showed that an increase in IL-6 induced by stress inhibited GABAA receptors in DMH neurons by activating the JAK/STAT signaling pathway, while specific inhibition of the JAK/STAT signaling pathway using AG490 obviously reduced DMH neuronal activity and improved heart rate variability in rats. These findings suggest that IL-6 regulates the expression of GABAA receptors via the activation of the JAK/STAT pathway in the DMH, which may be an important cause of heart rate variability in stressed rats.
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