Rapid dissemination of alpha-synuclein seeds through neural circuits in an in-vivo prion-like seeding experiment

Acta Neuropathologica Communications
Ayami OkuzumiNobuyuki Nukina

Abstract

Accumulating evidence suggests that the lesions of Parkinson's disease (PD) expand due to transneuronal spreading of fibrils composed of misfolded alpha-synuclein (a-syn), over the course of 5-10 years. However, the precise mechanisms and the processes underlying the spread of these fibril seeds have not been clarified in vivo. Here, we investigated the speed of a-syn transmission, which has not been a focus of previous a-syn transmission experiments, and whether a-syn pathologies spread in a neural circuit-dependent manner in the mouse brain. We injected a-syn preformed fibrils (PFFs), which are seeds for the propagation of a-syn deposits, either before or after callosotomy, to disconnect bilateral hemispheric connections. In mice that underwent callosotomy before the injection, the propagation of a-syn pathology to the contralateral hemisphere was clearly reduced. In contrast, mice that underwent callosotomy 24 h after a-syn PFFs injection showed a-syn pathology similar to that seen in mice without callosotomy. These results suggest that a-syn seeds are rapidly disseminated through neuronal circuits immediately after seed injection, in a prion-like seeding experiment in vivo, although it is believed that clinical a-syn pathol...Continue Reading

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Citations

Sep 27, 2019·Journal of Movement Disorders·Hyun Kyung ChungSeung-Jae Lee
Feb 13, 2020·Current Protocols in Neuroscience·Mikko AiravaaraAndrii Domanskyi
Apr 22, 2019·Acta Neuropathologica·Javier Alegre-AbarrateguiChristos Proukakis
Mar 24, 2020·Brain : a Journal of Neurology·Yutaka OjiNobutaka Hattori
May 12, 2020·Frontiers in Pharmacology·Mónica Gómez-BenitoRosario Moratalla
Sep 5, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Yvette C WongLaura A Volpicelli-Daley
Jun 20, 2019·Frontiers in Neurology·Susanne Fonseca SantosAntonio Pereira
May 13, 2020·International Journal of Molecular Sciences·Akio MoriNobutaka Hattori
Jan 7, 2021·International Journal of Molecular Sciences·Kazuya MatsuoKohji Fukunaga
Nov 13, 2020·Science Advances·Martin T HenrichD James Surmeier
Jan 13, 2021·Toxins·Charenya Anandan, Joseph Jankovic
Apr 5, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Jun UedaRyosuke Takahashi
Dec 15, 2020·Neuroscience Research·Junya KasaharaNobuyuki Nukina
Jul 9, 2020·ACS Omega·Gabriela HenríquezMahesh Narayan
Sep 14, 2021·Frontiers in Neuroscience·Amaryllis E HillPhilip W J Burnet

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Methods Mentioned

BETA
dissection

Software Mentioned

Amyg
Hybrid Cell Count
ZEN

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