Experience-dependent grooming microstructure alterations and gastrointestinal dysfunction in the SAPAP3 knockout mouse model of compulsive behaviour.

Autor: Wilson C; Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia., Gattuso JJ; Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia., Kuznetsova M; Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia., Li S; Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia., Connell S; Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia., Choo JM; Microbiome and Host Health, South Australian Health and Medical Research Institute, Adelaide, SA 5001, Australia; Infection and Immunity, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, Australia., Rogers GB; Microbiome and Host Health, South Australian Health and Medical Research Institute, Adelaide, SA 5001, Australia; Infection and Immunity, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, Australia., Gubert C; Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia., Hannan AJ; Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia., Renoir T; Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia. Electronic address: thibault.renoir@florey.edu.au.
Jazyk: angličtina
Zdroj: Journal of affective disorders [J Affect Disord] 2024 Oct 15; Vol. 363, pp. 520-531. Date of Electronic Publication: 2024 Jul 21.
DOI: 10.1016/j.jad.2024.07.143
Abstrakt: Background: Compulsive- and anxiety-like behaviour can be efficiently modelled in SAPAP3 knockout (KO) mice, a preclinical model of relevance to obsessive-compulsive disorder (OCD). Although there is emerging evidence in the clinical literature of gastrointestinal dysfunction in OCD, no previous studies have investigated gut function in preclinical models of relevance to OCD. Similarly, the effects of voluntary exercise (EX) or environmental enrichment (EE) have not yet been explored in this context.
Method: We comprehensively phenotyped the SAPAP3 KO mouse model, including the assessment of grooming microstructure, anxiety- and depressive-like behaviour, and gastrointestinal function. Mice were exposed to either standard housing (SH), exercise (EX, provided by giving mice access to running wheels), or environmental enrichment (EE) for 4 weeks to investigate the effects of enriched housing conditions in this animal model relevant to OCD.
Findings: Our study is the first to assess grooming microstructure, perseverative locomotor activity, and gastrointestinal function in SAPAP3 KO mice. We are also the first to report a sexually dimorphic effect of grooming in young-adult SAPAP3 KO mice; along with changes to grooming patterning and indicators of gut dysfunction, which occurred in the absence of gut dysbiosis in this model. Overall, we found no beneficial effects of voluntary exercise or environmental enrichment interventions in this mouse model; and unexpectedly, we revealed a deleterious effect of wheel-running exercise on grooming behaviour. We suspect that the detrimental effects of experimental housing in our study may be indicative of off-target effects of stress-a conclusion that warrants further investigation into the effects of chronic stress in this preclinical model of compulsive behaviour.
Competing Interests: Declaration of competing interest The authors have nothing to disclose.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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