L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease

Cell therapy is a promising treatment for Parkinson’s disease (PD), however clinical trials to date have shown relatively low survival and significant patient-to-patient variability. Glucagon Like Peptide-1 receptor (GLP-1R) agonists have potential neuroprotective effects on endogenous dopaminergic...

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Autores principales:	Osama F. Elabi, Jeffrey S. Davies, Emma L. Lane
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	exendin-4 liraglutide L-dopa cell transplantation neuroprotection Parkinson Disease Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/7737bd875e064af7a8c6239e9244d68f
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spelling	oai:doaj.org-article:7737bd875e064af7a8c6239e9244d68f2021-11-25T17:55:36ZL-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease10.3390/ijms2222123461422-00671661-6596https://doaj.org/article/7737bd875e064af7a8c6239e9244d68f2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12346https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Cell therapy is a promising treatment for Parkinson’s disease (PD), however clinical trials to date have shown relatively low survival and significant patient-to-patient variability. Glucagon Like Peptide-1 receptor (GLP-1R) agonists have potential neuroprotective effects on endogenous dopaminergic neurons. This study explores whether these agents could similarly support the growth and survival of newly transplanted neurons. 6-OHDA lesioned Sprague Dawley rats received intra-striatal grafts of dopaminergic ventral mesencephalic cells from embryonic day 14 Wistar rat embryos. Transplanted rats then received either saline or L-dopa (12 mg/kg) administered every 48 h prior to, and following cell transplantation. Peripheral GLP-1R agonist administration (exendin-4, 0.5 μg/kg twice daily or liraglutide, 100 μg/kg once daily) commenced immediately after cell transplantation and was maintained throughout the study. Graft survival increased under administration of exendin-4, with motor function improving significantly following treatment with both exendin-4 and liraglutide. However, this effect was not observed in rats administered with L-dopa. In contrast, L-dopa treatment with liraglutide increased graft volume, with parallel increases in motor function. However, this improvement was accompanied by an increase in leukocyte infiltration around the graft. The co-administration of L-dopa and exendin-4 also led to indicators of insulin resistance not seen with liraglutide, which may underpin the differential effects observed between the two GLP1-R agonists. Overall, there may be some benefit to the supplementation of grafted patients with GLP-1R agonists but the potential interaction with other pharmacological treatments needs to be considered in more depth.Osama F. ElabiJeffrey S. DaviesEmma L. LaneMDPI AGarticleexendin-4liraglutideL-dopacell transplantationneuroprotectionParkinson DiseaseBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12346, p 12346 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	exendin-4 liraglutide L-dopa cell transplantation neuroprotection Parkinson Disease Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	exendin-4 liraglutide L-dopa cell transplantation neuroprotection Parkinson Disease Biology (General) QH301-705.5 Chemistry QD1-999 Osama F. Elabi Jeffrey S. Davies Emma L. Lane L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease
description	Cell therapy is a promising treatment for Parkinson’s disease (PD), however clinical trials to date have shown relatively low survival and significant patient-to-patient variability. Glucagon Like Peptide-1 receptor (GLP-1R) agonists have potential neuroprotective effects on endogenous dopaminergic neurons. This study explores whether these agents could similarly support the growth and survival of newly transplanted neurons. 6-OHDA lesioned Sprague Dawley rats received intra-striatal grafts of dopaminergic ventral mesencephalic cells from embryonic day 14 Wistar rat embryos. Transplanted rats then received either saline or L-dopa (12 mg/kg) administered every 48 h prior to, and following cell transplantation. Peripheral GLP-1R agonist administration (exendin-4, 0.5 μg/kg twice daily or liraglutide, 100 μg/kg once daily) commenced immediately after cell transplantation and was maintained throughout the study. Graft survival increased under administration of exendin-4, with motor function improving significantly following treatment with both exendin-4 and liraglutide. However, this effect was not observed in rats administered with L-dopa. In contrast, L-dopa treatment with liraglutide increased graft volume, with parallel increases in motor function. However, this improvement was accompanied by an increase in leukocyte infiltration around the graft. The co-administration of L-dopa and exendin-4 also led to indicators of insulin resistance not seen with liraglutide, which may underpin the differential effects observed between the two GLP1-R agonists. Overall, there may be some benefit to the supplementation of grafted patients with GLP-1R agonists but the potential interaction with other pharmacological treatments needs to be considered in more depth.
format	article
author	Osama F. Elabi Jeffrey S. Davies Emma L. Lane
author_facet	Osama F. Elabi Jeffrey S. Davies Emma L. Lane
author_sort	Osama F. Elabi
title	L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease
title_short	L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease
title_full	L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease
title_fullStr	L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease
title_full_unstemmed	L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease
title_sort	l-dopa-dependent effects of glp-1r agonists on the survival of dopaminergic cells transplanted into a rat model of parkinson disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7737bd875e064af7a8c6239e9244d68f
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L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease

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