Regulation of the central amygdala on intestinal motility and behavior via the lateral hypothalamus in irritable bowel syndrome model mice

© 2022 John Wiley & Sons Ltd..

BACKGROUND: Impaired bidirectional communication between the gastrointestinal tract and the central nervous system (CNS) is closely related to the development of irritable bowel syndrome (IBS). Studies in patients with IBS have also shown significant activation of the hypothalamus and amygdala. However, how neural circuits of the CNS participate in and process the emotional and intestinal disorders of IBS remains unclear.

METHODS: The GABAergic neural pathway projecting from the central amygdala (CeA) to the lateral hypothalamus (LHA) in mice was investigated by retrograde tracking combined with fluorescence immunohistochemistry. Anxiety, depression-like behavior, and intestinal motility were observed in the water-immersion restraint stress group and the control group. Furthermore, the effects of the chemogenetic activation of the GABAergic neural pathway of CeA-LHA on behavior and intestinal motility, as well as the co-expression of orexin-A and c-Fos in the LHA, were explored.

KEY RESULTS: In our study, Fluoro-Gold retrograde tracking combined with fluorescence immunohistochemistry showed that GABAergic neurons in the CeA were projected to the LHA. The microinjection of the gamma-aminobutyric acid (GABA) receptor antagonist into the LHA relieved anxiety, depression-like behavior, and intestinal motility disorder in the IBS mice. The chemogenetic activation of GABAergic neurons in the CeA-LHA pathway led to anxiety, depression-like behavior, and intestinal motility disorder. In addition, GABAergic neurons in the CeA-LHA pathway inhibited the expression of orexin-A in the LHA, and orexin-A was co-expressed with GABAA receptors.

CONCLUSIONS & INFERENCES: The CeA-LHA GABAergic pathway might participate in the occurrence and development of IBS by regulating orexin-A neurons.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:35

Enthalten in:

Neurogastroenterology and motility - 35(2023), 2 vom: 24. Feb., Seite e14498

Sprache:

Englisch

Beteiligte Personen:

He, Xiaoman [VerfasserIn]
Ji, Pengfei [VerfasserIn]
Guo, Ruixiao [VerfasserIn]
Ming, Xing [VerfasserIn]
Zhang, Hongfei [VerfasserIn]
Yu, Lizheng [VerfasserIn]
Chen, Ziyi [VerfasserIn]
Gao, Shengli [VerfasserIn]
Guo, Feifei [VerfasserIn]

Links:

Volltext

Themen:

Central amygdala
GABA Antagonists
Gamma-aminobutyric acid
Irritable bowel syndrome
Journal Article
Lateral hypothalamus
Orexin-A
Orexins
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 01.02.2023

Date Revised 22.02.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1111/nmo.14498

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM349219559