The Absence of Gastrointestinal Redox Dyshomeostasis in the Brain-First Rat Model of Parkinson’s Disease Induced by Bilateral Intrastriatal 6-Hydroxydopamine

Scientific paper - Original scientific paper

• Author: Jan Homolak
• Author: Mihovil Joja
• Author: Gracia Grabaric
• Author: Emiliano Schiatti
• Author: Davor Virag
• Author: Ana Babić Perhoč
• Author: Ana Knezović
• Author: Jelena Osmanović Barilar
• Author: Melita Šalkovic-Petrišić
• Author's institution: University of Zagreb; School of Medicine; (Department of Pharmacology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Pharmacology

Abstract (english)

The gut-brain axis plays an important role in Parkinson’s disease (PD) by acting as a route for vagal propagation of aggregated α-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-weight thiols, and protein sulfhydryls, the activity of total and Mn/Fe superoxide dismutases, and total and azide-insensitive catalase/peroxidase were measured. Both univariate and multivariate models analyzing redox biomarkers indicate that significant disturbances in gastrointestinal redox balance are not present. The findings demonstrate that motor impairment observed in the brain-first 6-OHDA model of PD can occur without concurrent redox imbalances in the gastrointestinal system.

• Keywords (english): Animals; Brain / drug effects; Brain / metabolism; Brain / pathology; Corpus Striatum / drug effects; Corpus Striatum / metabolism; Corpus Striatum / pathology; Disease Models, Animal; Gastrointestinal Tract / drug effects; Gastrointestinal Tract / metabolism; Gastrointestinal Tract / pathology; Homeostasis* / drug effects; Male; Oxidation-Reduction / drug effects; Oxidative Stress / drug effects; Oxidopamine / pharmacology; Parkinson Disease / metabolism; Parkinson Disease / pathology; Rats; Rats, Wistar
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Molecular Neurobiology
• Numbering: vol. 61, no. 8, pp. 5481-5493
• p-ISSN: 0893-7648
• e-ISSN: 1559-1182
• DOI: https://doi.org/10.1007/s12035-023-03906-7
• URN:NBN: urn:nbn:hr:105:674241
• Publication: 2024-01-10
• Project: Number: IP-2018-01-8938; Title (croatian): Mehanizmi nutrijentom posredovanih učinaka endogenog glukagonu sličnog peptida-1 na kognitivne i metaboličke poremećaje u eksperimentalnim modelima neurodegenerativnih bolesti; Title (english): Mechanisms of nutrient-mediated effects of endogenous glucagone-like peptide -1 on cognitive and metabolic alterations in experimental models of neurodegenerative disorders; Acronym: NutrientGLP-1; Leader: Melita Šalković-Petrišić; Jurisdiction: Croatia; Funding stream: Research Projects
• Project: Number: KK.01.1.1.01.0007; Title (croatian): Znanstveni centar izvrsnosti - eksperimentalna i klinička istraživanja hipoksijsko-ishemijskog oštećenja mozga u perinatalnoj i odrasloj dobi; Title (english): Scientific center of excellence - Experimental and clinical research of hypoxic-ischemic brain damage in perinatal and adulthood; Acronym: ZCI-NEURO; Leader: Miloš Judaš; Jurisdiction: eu; Funding stream: European Regional Development Fund
• Document URL: https://link.springer.com/10.1007/s12035-023-03906-7
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-12-11 14:44:50