Nigral overexpression of α-synuclein in a rat Parkinson's disease model indicates alterations in the enteric nervous system and the gut microbiome
Autor: | Sarah M. O’Donovan, Aideen M. Sullivan, Niall P. Hyland, Yvonne M. Nolan, Cora O'Neill, Olivia F. O’Leary, Susan A. Joyce, Erin K. Crowley, Orla O'Sullivan, David Clarke, Suzanne Timmons, Jillian R.M. Brown |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty Parkinson's disease Physiology animal diseases Gut–brain axis Genetic Vectors Biology Gut flora Transfection digestive system Enteric Nervous System Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Parkinsonian Disorders Internal medicine medicine Animals Humans Neurochemistry Microbiome Myenteric plexus Injections Intraventricular Intestinal permeability Endocrine and Autonomic Systems Gastroenterology biology.organism_classification medicine.disease nervous system diseases Gastrointestinal Microbiome Rats Substantia Nigra 030104 developmental biology Endocrinology nervous system alpha-Synuclein Enteric nervous system Rats Transgenic 030217 neurology & neurosurgery |
Zdroj: | Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility SocietyREFERENCE. 32(1) |
ISSN: | 1365-2982 |
Popis: | Background A hallmark feature of Parkinson's disease (PD) is the build-up of α-synuclein protein aggregates throughout the brain; however α-synuclein is also expressed in enteric neurons. Gastrointestinal (GI) symptoms and pathology are frequently reported in PD, including constipation, increased intestinal permeability, glial pathology, and alterations to gut microbiota composition. α-synuclein can propagate through neuronal systems but the site of origin of α-synuclein pathology, whether it be the gut or the brain, is still unknown. Physical exercise is associated with alleviating symptoms of PD and with altering the composition of the gut microbiota. Methods This study investigated the effects of bilateral nigral injection of adeno-associated virus (AAV)-α-synuclein on enteric neurons, glia and neurochemistry, the gut microbiome, and bile acid metabolism in rats, some of whom were exposed to voluntary exercise. Key results Nigral overexpression of α-synuclein resulted in significant neuronal loss in the ileal submucosal plexus with no change in enteric glia. In contrast, the myenteric plexus showed a significant increase in glial expression, while neuronal numbers were maintained. Concomitant alterations were observed in the gut microbiome and related bile acid metabolism. Voluntary running protected against neuronal loss, increased enteric glial expression, and modified gut microbiome composition in the brain-injected AAV-α-synuclein PD model. Conclusions and inferences These results show that developing nigral α-synuclein pathology in this PD model exerts significant alterations on the enteric nervous system (ENS) and gut microbiome that are receptive to modification by exercise. This highlights brain to gut communication as an important mechanism in PD pathology. |
Databáze: | OpenAIRE |
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