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: | , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/7737bd875e064af7a8c6239e9244d68f |
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| Sumario: | 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. |
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