Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates
Open accessAbstract
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.
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A recent study did not find pathological damage to a-synuclein in the vagus nerve in an animal model of Parkinson's disease, which does not support the hypothesis that a-synuclein pathology is transmitted through the vagus nerve and the dorsal motor nucleus of the vagus nerve.
“Remarkably, a recent study did not find pathological damage to a-synuclein in the vagus nerve in an animal model of Parkinson's disease, which does not support the hypothesis that a-synuclein pathology is transmitted through the vagus nerve and the dorsal motor nucleus of the vagus nerve.140”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [140]
Patient-derived α-synuclein aggregates are able to induce nigrostriatal lesions and ENS pathology after either enteric or striatal injection in a non-human primate model (baboon monkeys), showing the role of the gut-brain axis in the propagation of Parkinson's disease.
“The latter study did show that patient-derived α-synuclein aggregates are able to induce nigrostriatal lesions and ENS pathology after either enteric or striatal injection in a non-human primate model (baboon monkeys), thus showing the role of the gut-brain axis in the propagation of Parkinson's disease.”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [400]
Arotcarena and colleagues did not find α-synuclein pathological lesions in the vagal nerve, thus arguing against the hypothesis that the vagal nerve is involved in the transmission of α-synuclein pathology.
“However, Arotcarena and colleagues [400] did not find α-synuclein pathological lesions in the vagal nerve, thus arguing against the hypothesis that the vagal nerve is involved in the transmission of α-synuclein pathology.”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [400]
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- Authors
- Arotcarena, M.-L., Dovero, S., Prigent, A., Bourdenx, M., Camus, S., Porras, G., Thiolat, M.-L., Tasselli, M., Aubert, P., Kruse, N., Mollenhauer, B., Trigo Damas, I., Estrada, C., Garcia-Carrillo, N., Vaikath, N. N., El-Agnaf, O. M. A., Herrero, M. T., Vila, M., Obeso, J. A., Derkinderen, P., Dehay, B., & Bezard, E.
- Affiliations
- University of Bordeaux, Neurodegenerative Diseases Institute, UMR 5293, F-33000 Bordeaux, France
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Universitätsmedizin Göttingen (DE)
- HM CINAC, HM Puerta del Sur, San Pablo University Madrid, E-28938 Mostoles, Spain
- Instituto Murciano de Investigación Biosanitaria (ES)
- Centro Experimental en Investigaciones Biomédica (CEIB), University of Murcia, Murcia, Spain
- Hamad bin Khalifa University (QA)
- Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Education City, Qatar
- Clinical and Experimental Neuroscience Unit, School of Medicine, Biomedical Research Institute of Murcia (IMIB), University of Murcia, Campus Mare Nostrum, 30100 Murcia, Spain
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Universidad San Pablo CEU (ES)
- Corresponding author
- Bourdenx, Mathieu
- Dehay, Benjamin
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-05-01
- Volume
- 143
- Issue
- 5
- Pages
- 1462-1475
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W3022308463
- Cited by
- 210
- References
- 29
- Citations by year
- 2026: 15 · 2025: 32 · 2024: 28 · 2023: 40 · 2022: 39 · 2021: 49 · 2020: 6
- FWCI
- 14.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Hispana (publishedVersion, cc-by-nc-nd)
- HAL (submittedVersion)
- Funders
- The University of Bordeaux
- the Centre National de la Recherche Scientifique
- Michael J Fox Foundation (2013-8499)
- Fundacion de Investigacion HM Hospitales
- Fundación Séneca (FS19540/PI/14)
- Simone and Cino Del Duca Prize
- French Academy of Sciences
- Ministère de l’Enseignement Supérieur et de la Recherche
- France Parkinson Foundation
- CECAP
- MINECO/AEI/FEDER-UE (SAF2015-67239-P)
- Bordeaux Imaging Center
- national infrastructure France BioImaging (ANR-10INBS-04-0)
- Biochemistry and Biophysics Platform of the Bordeaux Neurocampus at the Bordeaux University
- LABEX BRAIN (ANR-10-LABX-43)
- Brain Bank GIE NeuroCEB (0033-00011)
- France Alzheimer
- Connaître les Syndromes Cérébelleux
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Parkinson's disease, synucleinopathies, alpha-synuclein, gut-brain axis, enteric nervous system, vagus nerve, Lewy bodies, nigrostriatal lesion, nonhuman primate model, dorsal motor nucleus of the vagus
- MeSH terms
- Aged, Animals, Brain, Female, Humans, Male, Papio, Parkinson Disease, Vagus Nerve, Neuroimmunomodulation, Lewy Bodies, Enteric Nervous System, alpha-Synuclein
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