Nigral overexpression of α‐synuclein in a rat Parkinson’s disease model indicates alterations in the enteric nervous system and the gut microbiome

2019 ◽  
Vol 32 (1) ◽  
Author(s):  
Sarah M. O’Donovan ◽  
Erin K. Crowley ◽  
Jillian R.‐M. Brown ◽  
Orla O’Sullivan ◽  
Olivia F. O’Leary ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Gut Microbiome ◽  
Disease Model

scholarly journals The Baseline Structure of the Enteric Nervous System and Its Role in Parkinson’s Disease

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 732
Author(s):  
Gianfranco Natale ◽  
Larisa Ryskalin ◽  
Gabriele Morucci ◽  
Gloria Lazzeri ◽  
Alessandro Frati ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Gi Tract ◽  
Multiple Control ◽  
Fine Control ◽  
The Central Nervous System ◽  
Degenerative Alterations ◽  
Comprehensive Classification

The gastrointestinal (GI) tract is provided with a peculiar nervous network, known as the enteric nervous system (ENS), which is dedicated to the fine control of digestive functions. This forms a complex network, which includes several types of neurons, as well as glial cells. Despite extensive studies, a comprehensive classification of these neurons is still lacking. The complexity of ENS is magnified by a multiple control of the central nervous system, and bidirectional communication between various central nervous areas and the gut occurs. This lends substance to the complexity of the microbiota–gut–brain axis, which represents the network governing homeostasis through nervous, endocrine, immune, and metabolic pathways. The present manuscript is dedicated to identifying various neuronal cytotypes belonging to ENS in baseline conditions. The second part of the study provides evidence on how these very same neurons are altered during Parkinson’s disease. In fact, although being defined as a movement disorder, Parkinson’s disease features a number of degenerative alterations, which often anticipate motor symptoms. Among these, the GI tract is often involved, and for this reason, it is important to assess its normal and pathological structure. A deeper knowledge of the ENS is expected to improve the understanding of diagnosis and treatment of Parkinson’s disease.

scholarly journals Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates

Brain ◽  
2020 ◽  
Vol 143 (5) ◽  
pp. 1462-1475 ◽  
Author(s):  
Marie-Laure Arotcarena ◽  
Sandra Dovero ◽  
Alice Prigent ◽  
Mathieu Bourdenx ◽  
Sandrine Camus ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Vagus Nerve ◽  
Enteric Nervous System ◽  
General Circulation ◽  
Motor Nucleus ◽  
Long Distance ◽  
Primate Model ◽  
Systemic Mechanism

Abstract In Parkinson’s disease, synucleinopathy is hypothesized to spread from the enteric nervous system, via the vagus nerve, to the CNS. Here, we compare, in baboon monkeys, the pathological consequences of either intrastriatal or enteric injection of α-synuclein-containing Lewy body extracts from patients with Parkinson’s disease. This study shows that patient-derived α-synuclein aggregates are able to induce nigrostriatal lesions and enteric nervous system pathology after either enteric or striatal injection in a non-human primate model. This finding suggests that the progression of α-synuclein pathology might be either caudo-rostral or rostro-caudal, varying between patients and disease subtypes. In addition, we report that α-synuclein pathological lesions were not found in the vagal nerve in our experimental setting. This study does not support the hypothesis of a transmission of α-synuclein pathology through the vagus nerve and the dorsal motor nucleus of the vagus. Instead, our results suggest a possible systemic mechanism in which the general circulation would act as a route for long-distance bidirectional transmission of endogenous α-synuclein between the enteric and the central nervous systems. Taken together, our study provides invaluable primate data exploring the role of the gut-brain axis in the initiation and propagation of Parkinson’s disease pathology and should open the door to the development and testing of new therapeutic approaches aimed at interfering with the development of sporadic Parkinson’s disease.

scholarly journals Enteric nervous system and Parkinson's disease

2011 ◽  
Vol 54 ◽  
pp. e311
Author(s):  
P. Derkinderen ◽  
T. Lebouvier ◽  
H. Pouclet ◽  
M. Neunlist
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Enteric Nervous System

Dopaminergic defect of enteric nervous system in Parkinson's disease patients with chronic constipation

The Lancet ◽  
1995 ◽  
Vol 346 (8979) ◽  
pp. 861-864 ◽  
Author(s):  
C Singaram ◽  
E.A Gaumnitz ◽  
C Torbey ◽  
W Ashraf ◽  
E.M.M Quigley ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Chronic Constipation

scholarly journals Seeding Propensity and Characteristics of Pathogenic αSyn Assemblies in Formalin-Fixed Human Tissue from the Enteric Nervous System, Olfactory Bulb, and Brainstem in Cases Staged for Parkinson’s Disease

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 139
Author(s):  
Alexis Fenyi ◽  
Charles Duyckaerts ◽  
Luc Bousset ◽  
Heiko Braak ◽  
Kelly Del Tredici ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Lewy Body ◽  
Lewy Body Disease ◽  
Fixed Tissue ◽  
Incidental Lewy Body Disease ◽  
Seeding Efficiency ◽  
Formalin Fixed

We investigated α-synuclein’s (αSyn) seeding activity in tissue from the brain and enteric nervous system. Specifically, we assessed the seeding propensity of pathogenic αSyn in formalin-fixed tissue from the gastric cardia and five brain regions of 29 individuals (12 Parkinson’s disease, 8 incidental Lewy body disease, 9 controls) using a protein misfolding cyclic amplification assay. The structural characteristics of the resultant αSyn assemblies were determined by limited proteolysis and transmission electron microscopy. We show that fixed tissue from Parkinson’s disease (PD) and incidental Lewy body disease (ILBD) seeds the aggregation of monomeric αSyn into fibrillar assemblies. Significant variations in the characteristics of fibrillar assemblies derived from different regions even within the same individual were observed. This finding suggests that fixation stabilizes seeds with an otherwise limited seeding propensity, that yield assemblies with different intrinsic structures (i.e., strains). The lag phase preceding fibril assembly for patients ≥80 was significantly shorter than in other age groups, suggesting the existence of increased numbers of seeds or a higher seeding potential of pathogenic αSyn with time. Seeding activity did not diminish in late-stage disease. No statistically significant difference in the seeding efficiency of specific regions was found, nor was there a relationship between seeding efficiency and the load of pathogenic αSyn in a particular region at a given neuropathological stage.

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