The GABAergic pathway from anterior cingulate cortex to lateral hypothalamus area regulates irritable bowel syndrome in mice and its underlying mechanism.

Autor: Guo R; Department of Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China., Gao S; Biomedical Center, Qingdao Medical College, Qingdao University, Qingdao, China., Feng X; Department of Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China., Liu H; Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, China., Ming X; Department of Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China., Sun J; Department of Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China., Luan X; Qingdao Medical College, Qingdao University, Qingdao, China., Liu Z; Qingdao Medical College, Qingdao University, Qingdao, China., Liu W; Qingdao Medical College, Qingdao University, Qingdao, China., Guo F; Department of Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2024 Sep; Vol. 168 (9), pp. 2814-2831. Date of Electronic Publication: 2024 Jun 15.
DOI: 10.1111/jnc.16150
Abstrakt: Irritable bowel syndrome (IBS), which is characterized by chronic abdominal pain, has a high global prevalence. The anterior cingulate cortex (ACC), which is a pivotal region involved in pain processing, should be further investigated regarding its role in the regulation of visceral sensitivity and mental disorders. A C57BL/6J mouse model for IBS was established using chronic acute combining stress (CACS). IBS-like symptoms were assessed using behavioral tests, intestinal motility measurements, and abdominal withdrawal reflex scores. Fluoro-Gold retrograde tracing and immunohistochemistry techniques were employed to investigate the projection of ACC gamma-aminobutyric acid-producing (GABAergic) neurons to the lateral hypothalamus area (LHA). Chemogenetic approaches enabled the selective activation or inhibition of the ACC-LHA GABAergic pathway. Enzyme-linked immunosorbent assay (ELISA) and western blot analyses were conducted to determine the expression of histamine, 5-hydroxytryptamine (5-HT), and transient receptor potential vanilloid 4 (TRPV4). Our findings suggest that CACS induced IBS-like symptoms in mice. The GABA type A receptors (GABAAR) within LHA played a regulatory role in modulating IBS-like symptoms. The chemogenetic activation of ACC-LHA GABAergic neurons elicited anxiety-like behaviors, intestinal dysfunction, and visceral hypersensitivity in normal mice; however, these effects were effectively reversed by the administration of the GABAAR antagonist Bicuculline. Conversely, the chemogenetic inhibition of ACC-LHA GABAergic neurons alleviated anxiety-like behaviors, intestinal dysfunction, and visceral hypersensitivity in the mouse model for IBS. These results highlight the crucial involvement of the ACC-LHA GABAergic pathway in modulating anxiety-like behaviors, intestinal motility alterations, and visceral hypersensitivity, suggesting a potential therapeutic strategy for alleviating IBS-like symptoms.
(© 2024 International Society for Neurochemistry.)
Databáze: MEDLINE
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