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Experience-dependent grooming microstructure alterations and gastrointestinal dysfunction in the SAPAP3 knockout
Carey Wilson1, James J Gattuso1, Maria Kuznetsova1
1Florey 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.
Journal of Affective Disorders
|July 23, 2024
Summary
SAPAP3 knockout mice, a model for obsessive-compulsive disorder (OCD), show altered grooming and gut dysfunction without gut dysbiosis. Exercise and enrichment did not improve behavior, with exercise worsening grooming, suggesting potential stress effects.
Area of Science:
- Neuroscience
- Gastroenterology
- Behavioral Science
Background:
- SAPAP3 knockout (KO) mice serve as a preclinical model for obsessive-compulsive disorder (OCD), exhibiting compulsive and anxiety-like behaviors.
- Clinical studies suggest a link between gastrointestinal dysfunction and OCD, but this has not been explored in preclinical OCD models.
- The impact of voluntary exercise (EX) or environmental enrichment (EE) on gut function in OCD models remains uninvestigated.
Purpose of the Study:
- To comprehensively phenotype SAPAP3 KO mice, assessing grooming, behavior, and gastrointestinal function.
- To investigate the effects of standard housing (SH), exercise (EX), and environmental enrichment (EE) on this OCD preclinical model.
Main Methods:
- Phenotyping included assessment of grooming microstructure, anxiety- and depressive-like behavior, and gastrointestinal function in SAPAP3 KO mice.
- Mice were housed in standard conditions, with access to running wheels (EX), or in enriched environments (EE) for four weeks.
Main Results:
- This study is the first to examine grooming microstructure, perseverative locomotor activity, and gastrointestinal function in SAPAP3 KO mice.
- A sexually dimorphic effect on grooming was observed in young-adult SAPAP3 KO mice, alongside altered grooming patterns and gut dysfunction indicators, without gut dysbiosis.
- Neither voluntary exercise nor environmental enrichment showed beneficial effects; exercise unexpectedly worsened grooming behavior, possibly due to stress-related off-target effects.
Conclusions:
- SAPAP3 KO mice display grooming alterations and gut dysfunction relevant to OCD, independent of gut dysbiosis.
- Environmental interventions like exercise and enrichment were ineffective and potentially detrimental in this model.
- Further research is needed to explore the role of chronic stress in this preclinical model of compulsive behavior.
