Effects of L-DOPA/benserazide co-treatment on colonic excitatory cholinergic motility and enteric inflammation following dopaminergic nigrostriatal neurodegeneration

Neuropharmacology
Carolina PellegriniMatteo Fornai

Abstract

The mainstay therapy for Parkinson's disease (PD) relies on L-3,4-dihydroxyphenylalanine (L-DOPA) plus a DOPA-decarboxylase inhibitor. However, their effects on colonic dysmotility and inflammation observed in PD are undetermined. This study examined the effects of L-DOPA plus benserazide (BE) on colonic motility and inflammation in rats with central nigrostriatal dopaminergic denervation. Neurodegeneration was induced by 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB). 6-OHDA animals were treated orally with L-DOPA/BE for 28 days, starting 28 days after 6-OHDA injection. At the end of treatment, in vivo colonic transit was evaluated by a radiologic assay. Electrically stimulated (ES) cholinergic contractions were recorded in vitro from colonic preparations, while acetylcholine release was measured in the incubation medium. Choline acetyltransferase (ChAT) and glial fibrillary acidic protein (GFAP) expression as well as eosinophil and mast cell density were examined in the colonic wall by immunohistochemistry. Colonic TNF and IL-1β levels were also assayed. 6-OHDA animals displayed: 1) decrease in in vivo colonic transit; 2) impairment of ES-stimulated cholinergic contractions; 3) decreased acetylcho...Continue Reading

Citations

Jun 30, 2018·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·C-Z LiuJ-X Zhu
Oct 2, 2019·Frontiers in Molecular Neuroscience·Qian-Qian ChenJia-Yi Li
Feb 11, 2020·Expert Opinion on Pharmacotherapy·Shilan MozaffariMohammad Abdollahi
May 4, 2021·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Hiroyuki NakamoriHikaru Hashitani

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