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Article

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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School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, UK
2
Institute of Life Sciences, School of Medicine, Swansea University, Swansea SA2 8PP, UK
*
Authors to whom correspondence should be addressed.
Academic Editor: Ana I. Rodríguez-Pérez
Int. J. Mol. Sci. 2021, 22(22), 12346; https://doi.org/10.3390/ijms222212346
Received: 24 September 2021 / Revised: 5 November 2021 / Accepted: 12 November 2021 / Published: 16 November 2021
(This article belongs to the Special Issue The Mechanism of Dopaminergic Neuron Degeneration/Survival)
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. View Full-Text
Keywords: exendin-4; liraglutide; L-dopa; cell transplantation; neuroprotection; Parkinson Disease exendin-4; liraglutide; L-dopa; cell transplantation; neuroprotection; Parkinson Disease
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MDPI and ACS Style

Elabi, O.F.; Davies, J.S.; Lane, E.L. L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease. Int. J. Mol. Sci. 2021, 22, 12346. https://doi.org/10.3390/ijms222212346

AMA Style

Elabi OF, Davies JS, Lane EL. 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. 2021; 22(22):12346. https://doi.org/10.3390/ijms222212346

Chicago/Turabian Style

Elabi, Osama F., Jeffrey S. Davies, and Emma L. Lane. 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, no. 22: 12346. https://doi.org/10.3390/ijms222212346

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