The absence of gastrointestinal redox dyshomeostasis in the brain-first rat model of Parkinson's disease induced by bilateral intrastriatal 6-hydroxydopamine

Homolak, J.; Joja, M.; Grabaric, G.; Schiatti, E.; Virag, D.; Babic Perhoc, A.; Knezovic, A.; Osmanovic Barilar, J.; Salkovic-Petrisic, M.

doi:10.1101/2022.08.22.504759

bioRxiv · 10.1101/2022.08.22.504759

The absence of gastrointestinal redox dyshomeostasis in the brain-first rat model of Parkinson's disease induced by bilateral intrastriatal 6-hydroxydopamine

Homolak, J.·Joja, M.·Grabaric, G.·Schiatti, E.·Virag, D.·Babic Perhoc, A.·Knezovic, A.·Osmanovic Barilar, J.·Salkovic-Petrisic, M.

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Abstract

The gut-brain axis plays an important role in Parkinsons disease (PD) by acting as a route for vagal propagation of aggregated -synuclein in the gut-first endophenotype and as a mediator of gastrointestinal dyshomeostasis via the nigro-vagal pathway in the brain-first endophenotype of the disease. One important mechanism by which the gut-brain axis may promote PD is by regulating gastrointestinal redox homeostasis as overwhelming evidence suggests that oxidative stress plays a key role in the etiopathogenesis and progression of PD and the gastrointestinal tract maintains redox homeostasis of the organism by acting as a critical barrier to environmental and microbiological electrophilic challenges. The present aim was to utilize the bilateral intrastriatal 6-hydroxydopamine (6-OHDA) brain-first PD model to study the effects of isolated central pathology on redox homeostasis of the gastrointestinal tract. Three-month-old male Wistar rats were either not treated (intact controls; CTR) or treated bilaterally intrastriatally with vehicle (CIS) or 6-OHDA (6-OHDA). Motor deficits were assessed with the rotarod performance test and the duodenum, ileum, and colon were dissected for biochemical analyses 12 weeks after the treatment. Lipid peroxidation, total antioxidant capacity, low-molecular thiols, and protein sulfhydryls, the activity of total and Mn/Fe superoxide dismutases, and total and azide-insensitive catalase/peroxidase were measured. Univariate and multivariate models of redox biomarkers provide solid evidence against the existence of pronounced gastrointestinal redox dyshomeostasis. The results indicate that the dysfunction of the nigro-vagal system and not motor deficit may be a key mediator of gastrointestinal dyshomeostasis in brain-first 6-OHDA-induced rodent models of PD.

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Homolak, J., Joja, M., Grabaric, G., Schiatti, E., Virag, D., Babic Perhoc, A., Knezovic, A., Osmanovic Barilar, J., Salkovic-Petrisic, M.. 2022-08-22. The absence of gastrointestinal redox dyshomeostasis in the brain-first rat model of Parkinson's disease induced by bilateral intrastriatal 6-hydroxydopamine. https://doi.org/10.1101/2022.08.22.504759

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