Rifaximin improves anxiety- and depression-like behaviors in rats by regulating NPY in the colon and mPFC
Qian Luo1, Haonan Li1, Yihe Wang2
1Department of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.
Abstract:
Growing evidence implicates the brain-gut axis in depression pathogenesis, though the underlying mechanisms remain elusive. This study investigated the antidepressant potential of rifaximin, a non-absorbable antibiotic, and its mechanisms via the brain-gut axis in a rat chronic unpredictable mild stress (CUMS) model. We found that CUMS induced anxiety- and depression-like behaviors, impaired colonic endocrine cell function, and downregulated neuropeptide Y (NPY) expression in both the colon and medial prefrontal cortex (mPFC). CUMS also altered neuronal activation and disrupted key neurotransmitter (GABA, Glu, 5-HT) balance in the mPFC. Rifaximin treatment ameliorated these behavioral deficits, restored colonic endocrine function, and increased NPY levels in both the colon and mPFC. Furthermore, it normalized CUMS-induced alterations in neuronal activation and neurotransmitter balance. Crucially, functional knockdown of NPY in the mPFC not only reduced colonic NPY expression in control rats but also abolished the anxiolytic effects of rifaximin in CUMS-treated rats. In summary, this study suggests that in the CUMS model, rifaximin can play an anxiolytic and antidepressant effect, and its mechanism may be related to the rifaximin's regulation on NPY mediated gut-brain axis between colon and mPFC.
Insights
Rifaximin, an antibiotic, shows antidepressant and anxiolytic effects in a rat model of depression. It works by restoring gut-brain axis function and neuropeptide Y (NPY) levels in the colon and medial prefrontal cortex.
Area of Science:
- Neuroscience
- Gastroenterology
- Pharmacology
Background:
- The brain-gut axis is increasingly implicated in depression, but mechanisms are unclear.
- Chronic unpredictable mild stress (CUMS) in rats models depression, causing behavioral and physiological changes.
Purpose of the Study:
- To investigate the antidepressant potential of rifaximin.
- To elucidate the mechanisms of rifaximin's action via the brain-gut axis in a CUMS rat model.
Main Methods:
- Rats were subjected to CUMS to induce depression-like behaviors.
- Rifaximin treatment was administered, and its effects on behavior, colonic function, and neuropeptide Y (NPY) levels were assessed.
- Neuronal activation and neurotransmitter balance in the medial prefrontal cortex (mPFC) were analyzed.
- NPY function was modulated via knockdown in the mPFC.
Main Results:
- CUMS induced anxiety, depression, impaired colonic function, and altered NPY levels and neurotransmitters (GABA, Glu, 5-HT) in the mPFC.
- Rifaximin ameliorated behavioral deficits, restored colonic function, and normalized NPY levels and neurotransmitter balance.
- Knocking down NPY in the mPFC abolished rifaximin's anxiolytic effects, highlighting NPY's role.
Conclusions:
- Rifaximin exhibits anxiolytic and antidepressant effects in the CUMS rat model.
- Rifaximin's mechanism involves regulating the NPY-mediated gut-brain axis between the colon and mPFC.
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