ArticleNeurogastroenterology and motility2012
Mice overexpressing wild-type human alpha-synuclein display alterations in colonic myenteric ganglia and defecation.
Article in Neurogastroenterology and motility, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 114 citations in OpenAlex.
- Preclinical evaluation of nitrated α-synuclein-specific CAR-Treg therapy in Parkinson's disease.Cell reports. Medicine · 2026Article
- C1q-dependent clearance of alpha-synuclein allows macrophages to transiently limit enteric synucleinopathy in male mice.Nature communications · 2026Article
- Ultrastructural perspectives on the enteric nervous system in Parkinson's disease.Frontiers in neuroscience · 2026Review
- Predicting CSF α-Synuclein Seed Amplification Assay Status From Demographics and Clinical Data.Neurology open access · 2025Article
- Alpha synuclein overexpression can drive microbiome dysbiosis in mice.Scientific reports · 2025Article
- TNBS colitis induces architectural changes and alpha-synuclein overexpression in mouse distal colon: A morphological study.Cell and tissue research · 2025Article
- Olfactory deficit and gastrointestinal dysfunction precede motor abnormalities in alpha-Synuclein G51D knock-in mice.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Gut-Brain Axis in Focus: Polyphenols, Microbiota, and Their Influence on α-Synuclein in Parkinson's Disease.Nutrients · 2024Review
- Relationship among Parkinson's disease, constipation, microbes, and microbiological therapy.World journal of gastroenterology · 2024Review
- Behavioral analysis of motor and non-motor impairment in rodent models of Parkinson's disease.Frontiers in aging neuroscience · 2024Review
- Experimental Animal Models of Prodromal Parkinson's Disease.Journal of Parkinson's disease · 2024Review
- Gut-Brain Axis Deregulation and Its Possible Contribution to Neurodegenerative Disorders.Neurotoxicity research · 2023Review
- Parkinson's disease and gut microbiota: from clinical to mechanistic and therapeutic studies.Translational neurodegeneration · 2023Review
- Amyloid-β mediates intestinal dysfunction and enteric neurons loss in Alzheimer's disease transgenic mouse.Cellular and molecular life sciences : CMLS · 2023Article
- Complement C1q-dependent engulfment of alpha-synuclein induces ENS-resident macrophage exhaustion and accelerates Parkinson's-like gut pathology.bioRxiv : the preprint server for biology · 2023Article
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- Gut microbiome and Parkinson's disease: Perspective on pathogenesis and treatment.Journal of advanced research · 2023Review
- Colonic Myenteric Plexus Neurodegeneration and Minor Colon Inflammation in Trimethyltin-induced Rat Model of Neurodegeneration.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2023Article
- Distinct Patterns of Gene Expression Changes in the Colon and Striatum of Young Mice Overexpressing Alpha-Synuclein Support Parkinson's Disease as a Multi-System Process.Journal of Parkinson's disease · 2023Article
- Role of rodent models in advancing precision medicine for Parkinson's disease.Handbook of clinical neurology · 2023Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPrevalent non-motor symptoms of Parkinson's disease (PD) include gastrointestinal motor impairments and advanced stage PD displays pathological aggregates of α-synuclein in colonic enteric neurons. We previously showed that 12 months old mice overexpressing human wild type (WT) α-synuclein under the Thy1 promoter (Thy1-aSyn) displayed colonic motor dysfunction. We investigated functional gut alterations at earlier ages and histological correlates.
methodsDefecation, gastric emptying (GE), and immunostaining for α-synuclein, peripheral choline acetyltransferase (pChAT), tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS), and vasoactive intestinal peptide (VIP) in distal colon myenteric plexuses were assessed in male Thy1-aSyn compared to littermate WT mice. KEY
resultsThy1-aSyn mice aged 2.5-3 or 7-8 months old had 81% and 55% reduction in fecal pellet output, respectively, in the first 15 min of exposure to a novel environment. The reduction remained significant in the older group for 2-h, and subsequent refeeding resulted also in a 60% and 69% reduction of defecation in the first hour, respectively. Thy1-aSyn mice (8-10 months) displayed increased α-synuclein in the myenteric plexuses with abundant varicose terminals surrounding pChAT-immunoreactive (ir) neurons, and only a few, nNOS-ir neurons. There were no conspicuous changes in pChAT- and nNOS-ir neurons, or TH- and VIP-ir nerve fibers. Thy1-aSyn mice aged 4-18 months had normal GE. CONCLUSIONS & INFERENCES: The occurrence of over-production of pre-synaptic α-synuclein in colonic myenteric ganglia several months before the loss of striatal dopamine may provide an anatomical basis for interference with cholinergic neuronal activation, causing an early impairment in defecation to stimuli.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.