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 Alpha-synuclein alters the faecal viromes of rats in a gut-initiated model of Parkinson’s disease

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Stephen R. Stockdale ◽  
Lorraine A. Draper ◽  
Sarah M. O’Donovan ◽  
Wiley Barton ◽  
Orla O’Sullivan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Vagus Nerve ◽  
Enteric Nervous System ◽  
Neurological Disorder ◽  
Alpha Synuclein ◽  
Nerve Cells ◽  
Observational Period ◽  
The Brain

AbstractParkinson’s disease (PD) is a chronic neurological disorder associated with the misfolding of alpha-synuclein (α-syn) into aggregates within nerve cells that contribute to their neurodegeneration. Recent evidence suggests α-syn aggregation may begin in the gut and travel to the brain along the vagus nerve, with microbes potentially a trigger initiating α-syn misfolding. However, the effects α-syn alterations on the gut virome have not been investigated. In this study, we show longitudinal faecal virome changes in rats administered either monomeric or preformed fibrils (PFF) of α-syn directly into their enteric nervous system. Differential changes in rat viromes were observed when comparing monomeric and PFF α-syn, with alterations compounded by the addition of LPS. Changes in rat faecal viromes were observed after one month and did not resolve within the study’s five-month observational period. These results suggest that virome alterations may be reactive to host α-syn changes that are associated with PD development.

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 High-resolution ultrasound changes of the vagus nerve in idiopathic Parkinson’s disease (IPD): a possible additional index of disease

2021 ◽  
Author(s):  
F. Sartucci ◽  
T. Bocci ◽  
M. Santin ◽  
P. Bongioanni ◽  
G. Orlandi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Resolution ◽  
Vagus Nerve ◽  
Imaging Modality ◽  
Disease Stage ◽  
Motor Nucleus ◽  
Idiopathic Parkinson’S Disease ◽  
Idiopathic Parkinson's Disease ◽  
Additional Index

Abstract Background and rationale Histopathological studies revealed degeneration of the dorsal motor nucleus of the vagus nerve (VN) early in the course of idiopathic Parkinson’s disease (IPD). Degeneration of VN axons should be detectable by high-resolution ultrasound (HRUS) as a thinning of the nerve trunk. In order to establish if the VN exhibits sonographic signs of atrophy in IPD, we examined patients with IPD compared with age-matched controls. Material and methods We measured the caliber (cross-sectional area, CSA) and perimeter of the VN in 20 outpatients with IPD (8 females and 12 males; mean age 73.0 + 8.6 years) and in age-matched controls using HRUS. Evaluation was performed by blinded raters using an Esaote MyLab Gamma device in conventional B-Mode with an 8–19 MHz probe. Results In both sides, the VN CSA was significantly smaller in IPD outpatients than in controls (right 2.37 + 0.91, left 1.87 + 1.35 mm2 versus 6.0 + 1.33, 5.6 + 1.26 mm2; p <0.001), as well as the perimeter (right 5.06 + 0.85, left 4.78 + 1.74 mm versus 8.87 + 0.86, 8.58 + 0.97 mm; p <0.001). There were no significant correlations between VN CSA and age, the Hoehn and Yahr scale, L-dopa therapy, and disease duration. Conclusion Our findings provide evidence of atrophy of the VNs in IPD patients by HRUS. Moreover, HRUS of the VN represent a non-invasive easy imaging modality of screening in IPD patients independent of disease stage and duration and an interesting possible additional index of disease.

scholarly journals What Is the Evidence that Parkinson’s Disease Is a Prion Disorder, Which Originates in the Gut?

2018 ◽  
Vol 19 (11) ◽  
pp. 3573 ◽  
Author(s):  
Małgorzata Kujawska ◽  
Jadwiga Jodynis-Liebert
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Neurodegenerative Disorder ◽  
Human Subjects ◽  
Gastrointestinal Symptoms ◽  
Convincing Evidence ◽  
Substantia Nigra Pars Compacta ◽  
Motor Nucleus ◽  
The Brain

Parkinson’s disease (PD) is a neurodegenerative disorder resulting from degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). PD is characterized by motor dysfunctions as well as gastrointestinal symptoms and mental impairment. The pathological hallmark of PD is an accumulation of misfolded α-synuclein aggregates within the brain. The etiology of PD and related synucleinopathy is poorly understood, but recently, the hypothesis that α-synuclein pathology spreads in a prion-like fashion originating in the gut has gained much scientific attention. A crucial clue was the appearance of constipation before the onset of motor symptoms, gut dysbiosis and synucleinopathy in PD patients. Another line of evidence, demonstrating accumulation of α-synuclein within the peripheral autonomic nervous system (PANS), including the enteric nervous system (ENS), and the dorsal motor nucleus of the vagus (DMV) support the concept that α-synuclein can spread from the ENS to the brain by the vagus nerve. The decreased risk of PD following truncal vagotomy supports this. The convincing evidence of the prion-like behavior of α-synuclein came from postmortem observations that pathological α-synuclein inclusions appeared in healthy grafted neurons. In this review, we summarize the available data from human subjects’ research and animal experiments, which seem to be the most suggestive for explaining the hypotheses.

scholarly journals Neurophysiology of the brain stem in Parkinson’s disease

2019 ◽  
Vol 121 (5) ◽  
pp. 1856-1864 ◽  
Author(s):  
Cecilia Bove ◽  
R. Alberto Travagli
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Neuronal Degeneration ◽  
Alternative Hypothesis ◽  
Large Body ◽  
Substantia Nigra Pars Compacta ◽  
Clinical Feature ◽  
Motor Nucleus ◽  
Gi Symptoms

Parkinson’s disease (PD) is predominantly idiopathic in origin, and a large body of evidence indicates that gastrointestinal (GI) dysfunctions are a significant comorbid clinical feature; these dysfunctions include dysphagia, nausea, delayed gastric emptying, and severe constipation, all of which occur commonly before the onset of the well-known motor symptoms of PD. Based on a distinct distribution pattern of Lewy bodies (LB) in the enteric nervous system (ENS) and in the preganglionic neurons of the dorsal motor nucleus of the vagus (DMV), and together with the early onset of GI symptoms, it was suggested that idiopathic PD begins in the ENS and spreads to the central nervous system (CNS), reaching the DMV and the substantia nigra pars compacta (SNpc). These two areas are connected by a recently discovered monosynaptic nigro-vagal pathway, which is dysfunctional in rodent models of PD. An alternative hypothesis downplays the role of LB transport through the vagus nerve and proposes that PD pathology is governed by regional or cell-restricted factors as the leading cause of nigral neuronal degeneration. The purpose of this brief review is to summarize the neuronal electrophysiological findings in the SNpc and DMV in PD.

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
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