Spontaneous Graft-Induced Dyskinesias Are Independent of 5-HT Neurons and Levodopa Priming in a Model of Parkinson's Disease.
Spontaneous Graft-Induced Dyskinesias Are Independent of 5-HT Neurons and Levodopa Priming in a Model of Parkinson's Disease.
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DOI：
10.1002/mds.28856
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发表时间：
2022-03
影响因子：
8.6
通讯作者：
Lelos, Mariah J.
中科院分区：
文献类型：
--
作者：
Lane, Emma L.;Harrison, David J.;Ramos-Varas, Elena;Hills, Rachel;Turner, Sophie;Lelos, Mariah J.
关键词：
移植物诱导的运动障碍（GID）的风险是进展细胞移植作为帕金森病治疗的主要挑战。目前的理论暗示存在移植的5-羟色胺神经元、多巴胺释放热点、神经炎症和已建立的左旋多巴诱导的运动障碍。阐明胃肠道免疫缺陷的发生机制。新生脱敏，多巴胺去神经大鼠接受纹状体内移植的人胚胎干细胞（hESC）分化成腹侧中脑多巴胺能祖细胞（vmDA）（n = 15）或腹侧前脑细胞（n = 14）。在8只移植物存活的大鼠中，2只vmDA大鼠发生慢性自发性GID，在移植后30周观察到。GIDs受D2样受体拮抗剂抑制，不受5-HT 1A/1B/5-HT 6激动剂/拮抗剂影响。GID大鼠的移植物显示出更多的小胶质细胞活化，缺乏5-羟色胺神经元。这些发现反驳了目前认为大鼠不会发生自发性GID并且5-羟色胺神经元是病因的观点，而是表明GID可以在大鼠中由hESC衍生的多巴胺移植物诱导，并且关键的是，可以独立于先前的左旋多巴暴露和移植的5-羟色胺神经元而发生。版权所有© 2021作者。运动障碍由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版
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. To elucidate the mechanisms of GIDs. 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). 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. 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. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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影响因子：
64.8
作者：
Kriks, Sonja;Shim, Jae-Won;Piao, Jinghua;Ganat, Yosif M.;Wakeman, Dustin R.;Xie, Zhong;Carrillo-Reid, Luis;Auyeung, Gordon;Antonacci, Chris;Buch, Amanda;Yang, Lichuan;Beal, M. Flint;Surmeier, D. James;Kordower, Jeffrey H.;Tabar, Viviane;Studer, Lorenz
通讯作者：
Studer, Lorenz
影响因子：
5.9
作者：
Doi, Daisuke;Samata, Bumpei;Katsukawa, Mitsuko;Kikuchi, Tetsuhiro;Morizane, Asuka;Ono, Yuichi;Sekiguchi, Kiyotoshi;Nakagawa, Masato;Parmar, Malin;Takahashi, Jun
通讯作者：
Takahashi, Jun
影响因子：
6.1
作者：
Breger, Ludivine S.;Dunnett, Stephen B.;Lane, Emma L.
通讯作者：
Lane, Emma L.
DOI：
10.1007/s00702-017-1823-7
发表时间：
2018-08
期刊：
Journal of neural transmission (Vienna, Austria : 1996)
影响因子：
--
作者：
Pagano G;Niccolini F;Politis M
通讯作者：
Politis M
影响因子：
2.5
作者：
Chu, YP;Kompoliti, K;Kordower, JH
通讯作者：
Kordower, JH