Intestinal Barrier Dysfunction in the Absence of Systemic Inflammation Fails to Exacerbate Motor Dysfunction and Brain Pathology in a Mouse Model of Parkinson's Disease.
Parkinson's disease
dextran sodium sulfate (DSS)
gut-brain axis
intestinal hyperpermeability
microbiome
Journal
Frontiers in neurology
ISSN: 1664-2295
Titre abrégé: Front Neurol
Pays: Switzerland
ID NLM: 101546899
Informations de publication
Date de publication:
2022
2022
Historique:
received:
24
02
2022
accepted:
14
04
2022
entrez:
6
6
2022
pubmed:
7
6
2022
medline:
7
6
2022
Statut:
epublish
Résumé
Parkinson's disease (PD) is the second most common neurodegenerative disease associated with aging. PD patients have systemic and neuroinflammation which is hypothesized to contribute to neurodegeneration. Recent studies highlight the importance of the gut-brain axis in PD pathogenesis and suggest that gut-derived inflammation can trigger and/or promote neuroinflammation and neurodegeneration in PD. However, it is not clear whether microbiota dysbiosis, intestinal barrier dysfunction, or intestinal inflammation (common features in PD patients) are primary drivers of disrupted gut-brain axis in PD that promote neuroinflammation and neurodegeneration. To determine the role of microbiota dysbiosis, intestinal barrier dysfunction, and colonic inflammation in neuroinflammation and neurodegeneration in a genetic rodent model of PD [α-synuclein overexpressing (ASO) mice]. To distinguish the role of intestinal barrier dysfunction separate from inflammation, low dose (1%) dextran sodium sulfate (DSS) was administered in cycles for 52 days to ASO and control mice. The outcomes assessed included intestinal barrier integrity, intestinal inflammation, stool microbiome community, systemic inflammation, motor function, microglial activation, and dopaminergic neurons. Low dose DSS treatment caused intestinal barrier dysfunction (sugar test, histological analysis), intestinal microbiota dysbiosis, mild intestinal inflammation (colon shortening, elevated MPO), but it did not increase systemic inflammation (serum cytokines). However, DSS did not exacerbate motor dysfunction, neuroinflammation (microglial activation), or dopaminergic neuron loss in ASO mice. Disruption of the intestinal barrier without overt intestinal inflammation is not associated with worsening of PD-like behavior and pathology in ASO mice.
Identifiants
pubmed: 35665034
doi: 10.3389/fneur.2022.882628
pmc: PMC9159909
doi:
Types de publication
Journal Article
Langues
eng
Pagination
882628Informations de copyright
Copyright © 2022 Jackson, Engen, Forsyth, Shaikh, Naqib, Wilber, Frausto, Raeisi, Green, Bradaric, Persons, Voigt and Keshavarzian.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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