Indole induces anxiety-like behaviour in mice mediated by brainstem locus coeruleus activation.

Autor: Mir HD; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France., Yang Q; Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Brain Connectome and Behaviour, CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China., Maximin E; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France., Montardy Q; Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Brain Connectome and Behaviour, CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China., Ji S; Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Brain Connectome and Behaviour, CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China., Cheng Q; Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Brain Connectome and Behaviour, CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China., Shan X; Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Brain Connectome and Behaviour, CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China., Wang L; Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Brain Connectome and Behaviour, CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China., Naudon L; Université Paris-Saclay, INRAE, AgroParisTech, CNRS, Micalis Institute, Jouy-en-Josas, France., Rabot S; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France. Electronic address: Sylvie.Rabot@inrae.fr., Li L; Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Brain Connectome and Behaviour, CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China. Electronic address: saralilei@siat.ac.cn.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2024 Oct 01; Vol. 200, pp. 106606. Date of Electronic Publication: 2024 Jul 15.
DOI: 10.1016/j.nbd.2024.106606
Abstrakt: The gut microbiota produces metabolites that enrich the host metabolome and play a part in host physiology, including brain functions. Yet the biological mediators of this gut-brain signal transduction remain largely unknown. In this study, the possible role of the gut microbiota metabolite indole, originating from tryptophan, was investigated. Oral administration of indole to simulate microbial overproduction of this compound in the gut consistently led to impaired locomotion and anxiety-like behaviour in both C3H/HeN and C57BL/6J mice. By employing c-Fos protein expression mapping in mice, we observed a noticeable increase in brain activation within the dorsal motor nucleus of the vagus nerve (DMX) and the locus coeruleus (LC) regions in a dose-dependent manner. Further immune co-labelling experiments elucidated that the primary cells activated within the LC were tyrosine hydroxylase positive. To delve deeper into the mechanistic aspects, we conducted chemogenetic activation experiments on LC norepinephrine neurons with two doses of clozapine N-oxide (CNO). Low dose of CNO at 0.5 mg/kg induced no change in locomotion but anxiety-like behaviour, while high dose of CNO at 2 mg/kg resulted in locomotion impairment and anxiety-like behaviour. These findings support the neuroactive roles of indole in mediating gut-brain communication. It also highlights the LC as a novel hub in the gut-brain axis, encouraging further investigations.
Competing Interests: Declaration of competing interest The authors declare no competing interests.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
Externí odkaz: