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

Xuan Yu, Marine Persillet, Ling Zhang, Yu Zhang, Sun Xiuping, Xianglei Li, Gao Ran, Ludivine S. Breger, Sandra Dovero, Gregory Porras, Benjamin Dehay, Erwan Bezard, Chuan Qin
Neurobiology of Disease. 2021-01-01; : 105255
DOI: 10.1016/j.nbd.2021.105255

PubMed
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Yu X(1), Persillet M(2), Zhang L(1), Zhang Y(1), Xiuping S(1), Li X(1), Ran G(1), Breger LS(2), Dovero S(2), Porras G(2), Dehay B(2), Bezard E(3), Qin C(4).

Author information:
(1)NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering
Research Center for Experimental Animal Models of Human Critical Diseases, Peking
Union Medical College (PUMC) & Institute of Laboratory Animal Science, Chinese
Academy of Medical Science (CAMS), Beijing, China.
(2)Univ. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France.
(3)NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering
Research Center for Experimental Animal Models of Human Critical Diseases, Peking
Union Medical College (PUMC) & Institute of Laboratory Animal Science, Chinese
Academy of Medical Science (CAMS), Beijing, China; Univ. Bordeaux, CNRS, IMN, UMR
5293, F-33000 Bordeaux, France. Electronic address: .
(4)NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering
Research Center for Experimental Animal Models of Human Critical Diseases, Peking
Union Medical College (PUMC) & Institute of Laboratory Animal Science, Chinese
Academy of Medical Science (CAMS), Beijing, China. Electronic address:
.

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.

Copyright © 2021. Published by Elsevier Inc.

Conflict of interest statement: Declaration of Competing Interest E.B. is Chief Scientific Officer of Motac Neuroscience Ltd. All other authors declare no competing financial interests.

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