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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
,
Emma L. Lane
International Journal of Molecular Sciences, Volume: 22, Issue: 22, Start page: 12346
Swansea University Author:
Jeffrey Davies
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DOI (Published version): 10.3390/ijms222212346
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...
| Published in: | International Journal of Molecular Sciences |
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| ISSN: | 1422-0067 |
| Published: |
MDPI AG
2021
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa58729 |
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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. |
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| Keywords: |
exendin-4, liraglutide, L-dopa, cell transplantation, neuroprotection, Parkinson Disease |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
Iraqi government_ PhD sponsor Grant: SF4914_ account number at Cardiff University |
| Issue: |
22 |
| Start Page: |
12346 |