Striatal 6-hydroxydopamine lesion in rats induces dysregulation of the gut barrier.

Authors

Cassandra J Kaufhold, Kaylin A Pickle, Debanjana Das, Zara Akbari, Esteban D Lepe, Maia L Martin, Rachel Pilla, Rahul Srinivasan, Farida Sohrabji

Published in

Experimental neurology. Pages 116024. Sep 13, 2026. Epub Sep 13, 2026.

Abstract

Gastrointestinal (GI) dysfunction is a well-recognized prodromal feature of Parkinson's disease (PD), yet the mechanisms linking central dopaminergic (DA) neurodegeneration to gut pathology remain unclear. Previous studies have reported intestinal permeability and microbiome changes in toxin-based PD models, but the specific contribution of nigrostriatal injury to these outcomes is unknown. Here, we used the 6-hydroxydopamine (6-OHDA) rat model to determine whether selective loss of substantia nigra pars compacta (SNc) DA neurons disrupt gut barrier integrity and microbial homeostasis. Neurodegeneration was confirmed by progressive apomorphine-induced rotations and reduced tyrosine hydroxylase (TH) expression in the SNc and Dorsal Lateral Striatum (DLS). 6-OHDA lesioning led to increased circulating lipopolysaccharide (LPS) and intestinal fatty acid-binding protein (iFABP), consistent with impaired gut barrier function. Immunostaining for Villin, an actin-binding protein in microvilli, revealed no changes to the enterocyte brush border in either the ileum or colon. However, the tight junction protein zona occludens-1 (ZO-1) had marked reductions in both the ileum and more profoundly in the colon, indicating regional vulnerability. 6-OHDA-lesioned rats also exhibited alterations in specific gram-negative bacterial classes and reduced short-chain fatty acid levels (SCFAs). Together, these findings demonstrate that neurotrauma in the DA system can compromise gut integrity and microbial composition, supporting a brain-to-gut axis in PD pathophysiology and identifying gut barrier protection as a potential therapeutic target.

PMID:
42732868
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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