Serotonergic and dopaminergic mechanisms in graft-induced dyskinesia in a rat model of Parkinson's disease

Neurobiology of Disease
Eunju ShinManolo Carta

Abstract

Dyskinesia seen in the off-state, referred as graft-induced dyskinesia (GID), has emerged as a serious complication induced by dopamine (DA) cell transplantation in parkinsonian patients. Although the mechanism underlying the appearance of GID is unknown, in a recent clinical study the partial 5-HT(1A) agonist buspirone was found to markedly reduce GID in three grafted patients, who showed significant serotonin (5-HT) hyperinnervation in the grafted striatum in positron emission tomography scanning (Politis et al., 2010, 2011). Prompted by these findings, this study was performed to investigate the involvement of serotonin neurons in the appearance of GID in the rat 6-hydroxydopamine model. L-DOPA-primed rats received transplants of DA neurons only, DA plus 5-HT neurons or 5-HT neurons only into the lesioned striatum. In DA cell-grafted rats, with or without 5-HT neurons, but not in 5-HT grafts, GID was observed consistently after administration of amphetamine (1.5mg/kg, i.p.) indicating that grafted DA neurons are required to induce GID. Strikingly, a low dose of buspirone produced a complete suppression of GID. In addition, activation of 5-HT(1A) and 5-HT(1B) receptors by 8-OH-DPAT and CP 94253, known to inhibit the activity ...Continue Reading

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Citations

Oct 31, 2013·Proceedings of the National Academy of Sciences of the United States of America·Daniella RylanderBarbara Picconi
Feb 24, 2016·Frontiers in Cellular Neuroscience·Daniella Rylander Ottosson, Emma Lane
Feb 18, 2016·Parkinson's Disease·Elisabetta TronciManolo Carta
Sep 30, 2015·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Olle Lindvall
Sep 19, 2012·Stem Cells International·Julio C AguilaRosario Sanchez-Pernaute
Mar 27, 2015·Parkinson's Disease·Philippe HuotJonathan M Brotchie
Mar 23, 2017·Journal of Neural Transmission·Scott C Vermilyea, Marina E Emborg
Sep 13, 2014·Movement Disorders : Official Journal of the Movement Disorder Society·Anne Rosser, Clive N Svendsen
Aug 18, 2018·The European Journal of Neuroscience·Emma L Lane
Aug 21, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·C Warren OlanowJose A Obeso
Jul 6, 2013·Experimental Biology and Medicine·Ludivine S Breger, Emma L Lane
Jun 22, 2013·Movement Disorders : Official Journal of the Movement Disorder Society·Erwan BézardJosé A Obeso
Nov 13, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Emma L LaneMariah J Lelos

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