L-dopa-dependent effects of GLP-1R agonists on the survival of dopaminergic cells transplanted into a rat model of Parkinson disease

Elabi, Osama F., Davies, Jeffrey S. and Lane, Emma L. ORCID: https://orcid.org/0000-0001-8800-3764 2021. L-dopa-dependent effects of GLP-1R agonists on the survival of dopaminergic cells transplanted into a rat model of Parkinson disease. International Journal of Molecular Sciences 22 (22) , 12346. 10.3390/ijms222212346

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Abstract

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

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Additional Information:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/)
Publisher:	MDPI
ISSN:	1422-0067
Date of First Compliant Deposit:	30 November 2021
Date of Acceptance:	12 November 2021
Last Modified:	09 May 2023 19:49
URI:	https://orca.cardiff.ac.uk/id/eprint/145821

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