Valeric acid reduction by chitosan oligosaccharide induces autophagy in a Parkinson’s disease mouse model

Abstract

Parkinson’s disease (PD) is a central nervous system disease with the highest disability and mortality rate worldwide, and it is caused by a variety of factors. The most common medications for PD have side effects with limited therapeutic outcomes. Many studies have reported that chitosan oligosaccharide (COS) crossed blood-brain barrier to achieve a neuroprotective effect in PD. However, the role of COS in PD remains unclear. The present study demonstrated that COS increased dopaminergic neurons in the substantia nigra (SN) and ameliorated dyskinesia in a PD mouse model. Moreover, COS reduced gut microbial diversity and faecal short-chain fatty acids. Valeric acid supplementation enhanced the inflammatory response in the colon and SN, and it reversed COS - suppressed dopamine neurons damage. Autophagy was involved in COS modulating inflammation through valeric acid. These results suggest that COS reduces bacterial metabolites - valeric acid, which diminishes inflammation via activating autophagy, ultimately alleviating PD.

Keywords:

• Parkinson’s disease
• chitosan oligosaccharide
• valeric acid
• inflammation
• autophagy

Authors’ contributions

Methodology, R. C., K. L., Y. W., R.W.; Writing the manuscript, R.C.; Writing and Revision of the manuscript, and supervision, W.Z., Z. Y., J. Y., N. Z.; Acquisition and analysis of data, R. C., Y. W., K. L., L. S., R.W.; Funding acquisition and project administration: Z. Y., J. Y.

Disclosure statement

There is no conflict of interest in this submission. I declared on behalf of my co-authors that the work described here is original research that has not been published previously, and meet the criteria for authorship. All of the authors approved the manuscript for publication.

Data availability statement

The datasets generated during and/or analysed during the current study are available from the corresponding author Jinyuan Yan on reasonable request.

Additional information

Funding

This work was supported by National Natural Science Foundation of China [Nos. 31860274, 32260196]; Yunnan Provincial Science and Technology Department [Nos. 202101AT070251, 202301AY070001-239, 202307AB110046, 202005AC160058, 202101AZ070001-012, 202201AS070084, 202303AC100294]; Kunming Medical University Graduate Innovation Fund [No.2023S076].