Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Spontaneous graft-induced dyskinesias are independent of 5-HT neurons and levodopa priming in a model of Parkinson's disease

Lane, Emma L., Harrison, David J., Ramos-Varas, Elena, Hills, Rachel, Turner, Sophie and Lelos, Mariah J. 2021. Spontaneous graft-induced dyskinesias are independent of 5-HT neurons and levodopa priming in a model of Parkinson's disease. Movement Disorders 10.1002/mds.28856

[img] PDF - Published Version
Available under License Creative Commons Attribution.

Download (4MB)

Abstract

Background The risk of graft-induced dyskinesias (GIDs) presents a major challenge in progressing cell transplantation as a therapy for Parkinson's disease. Current theories implicate the presence of grafted serotonin neurons, hotspots of dopamine release, neuroinflammation and established levodopa-induced dyskinesia. Objective To elucidate the mechanisms of GIDs. Methods Neonatally desensitized, dopamine denervated rats received intrastriatal grafts of human embryonic stem cells (hESCs) differentiated into either ventral midbrain dopaminergic progenitor (vmDA) (n = 15) or ventral forebrain cells (n = 14). Results Of the eight rats with surviving grafts, two vmDA rats developed chronic spontaneous GIDs, which were observed at 30 weeks post-transplantation. GIDs were inhibited by D2-like receptor antagonists and not affected by 5-HT1A/1B/5-HT6 agonists/antagonists. Grafts in GID rats showed more microglial activation and lacked serotonin neurons. Conclusions These findings argue against current thinking that rats do not develop spontaneous GID and that serotonin neurons are causative, rather indicating that GID can be induced in rats by hESC-derived dopamine grafts and, critically, can occur independently of both previous levodopa exposure and grafted serotonin neurons.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Biosciences
Pharmacy
Additional Information: This is an open access article under the terms of the Creative Commons Attribution License
Publisher: Wiley
ISSN: 0885-3185
Funders: MRC, Parkinson's UK
Date of First Compliant Deposit: 12 November 2021
Date of Acceptance: 20 October 2021
Last Modified: 22 Nov 2021 14:41
URI: http://orca.cardiff.ac.uk/id/eprint/145473

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics