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Velusetrag rescues GI dysfunction, gut inflammation and dysbiosis in a mouse model of Parkinson’s disease
Velusetrag rescues GI dysfunction, gut inflammation and dysbiosis in a mouse model of Parkinson’s disease
- Source :
- npj Parkinson's Disease, Vol 9, Iss 1, Pp 1-15 (2023)
- Publication Year :
- 2023
- Publisher :
- Nature Portfolio, 2023.
-
Abstract
- Abstract In patients with Parkinson’s disease (PD), constipation is common, and it appears in a prodromal stage before the hallmark motor symptoms. The present study aimed to investigate whether Velusetrag, a selective 5‑HT4 receptor agonist, may be a suitable candidate to improve intestinal motility in a mouse model of PD. Five months old PrP human A53T alpha-synuclein transgenic (Tg) mice, which display severe constipation along with decreased colonic cholinergic transmission already at 3 months, were treated daily with the drug for 4 weeks. Velusetrag treatment reduced constipation by significantly stimulating both the longitudinal and circular-driven contractions and improved inflammation by reducing the level of serum and colonic IL1β and TNF-α and by decreasing the number of GFAP-positive glia cells in the colon of treated mice. No significant downregulation of the 5-HT4 receptor was observed but instead Velusetrag seemed to improve axonal degeneration in Tgs as shown by an increase in NF-H and VAChT staining. Ultimately, Velusetrag restored a well-balanced intestinal microbial composition comparable to non-Tg mice. Based on these promising data, we are confident that Velusetrag is potentially eligible for clinical studies to treat constipation in PD patients.
- Subjects :
- Neurology. Diseases of the nervous system
RC346-429
Subjects
Details
- Language :
- English
- ISSN :
- 23738057
- Volume :
- 9
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- npj Parkinson's Disease
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.033f9b868f44b3b9f1b3b747ced7510
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s41531-023-00582-1