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Evaluation of blood flow as a route for propagation in experimental synucleinopathy

Abstract : In Parkinson's disease, synucleinopathy is hypothesized to spread from the enteric nervous system, via the vagus nerve, to the central nervous system. Recent evidences collected in non-human primates challenge however the hypothesis of a transmission of α-synuclein (α-syn) pathology through the vagus nerve. Would the hypothesis whereby the bloodstream acts as a route for long-distance transmission of pathological α-syn hold true, an inter-individual transmission of synucleinopathy could occur via blood contact. Here, we used a parabiosis approach to join the circulatory systems of wild type and GFP transgenic C57BL/6 J mice, for which one of the partners parabiont received a stereotaxic intranigral injection of patient-derived α-syn aggregates. While the Lewy Body-receiving mice exhibited a loss of dopamine neurons and an increase in nigral S129 phosphorylated α-syn immunoreactivity, their parabiotic bloodstream-sharing partners did not show any trend for a lesion or change in S129 phosphorylated-α-syn levels. Altogether, our study suggests that, in the patient-derived α-synuclein aggregates-injected mouse model and within the selected time frame, the disease is not "transmitted" through the bloodstream.
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https://www.hal.inserm.fr/inserm-03105389
Contributor : Benjamin Dehay <>
Submitted on : Monday, January 11, 2021 - 9:49:45 AM
Last modification on : Tuesday, January 12, 2021 - 3:21:35 AM
Long-term archiving on: : Monday, April 12, 2021 - 6:25:59 PM

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Xuan Yu, Marine Persillet, Ling Zhang, Yu Zhang, Sun Xiuping, et al.. Evaluation of blood flow as a route for propagation in experimental synucleinopathy. Neurobiology of Disease, Elsevier, 2021, pp.105255. ⟨10.1016/j.nbd.2021.105255⟩. ⟨inserm-03105389⟩

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