L-dopa-dependent effects of GLP-1R agonists on the survival of dopaminergic cells transplanted into a rat model of Parkinson disease
| العنوان: | 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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| المؤلفون: | Emma Louise Lane, Jeffrey S. Davies, Osama F Elabi |
| المصدر: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 12346, p 12346 (2021) Volume 22 Issue 22 |
| بيانات النشر: | MDPI, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Gene Expression, Pharmacology, Cell therapy, Levodopa, Rats, Sprague-Dawley, Cell Movement, exendin-4, L-dopa, Leukocytes, Drug Interactions, Biology (General), Receptor, Spectroscopy, liraglutide, Dopaminergic, Graft Survival, Parkinson Disease, General Medicine, Computer Science Applications, Chemistry, Neuroprotective Agents, neuroprotection, Female, medicine.drug, Agonist, medicine.drug_class, QH301-705.5, Motor Activity, Glucagon, Neuroprotection, Catalysis, Article, Glucagon-Like Peptide-1 Receptor, Inorganic Chemistry, Dopaminergic Cell, medicine, Animals, Physical and Theoretical Chemistry, Parkinson Disease, Secondary, Rats, Wistar, cell transplantation, Oxidopamine, Molecular Biology, QD1-999, Liraglutide, business.industry, Dopaminergic Neurons, Organic Chemistry, Embryo, Mammalian, Corpus Striatum, Rats, Exenatide, Insulin Resistance, business |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::824de3e818ece0e82c46fb5c1bc97d48Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....824de3e818ece0e82c46fb5c1bc97d48 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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