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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

Osama F. Elabi, Jeffrey Davies Orcid Logo, Emma L. Lane

International Journal of Molecular Sciences, Volume: 22, Issue: 22, Start page: 12346

Swansea University Author: Jeffrey Davies Orcid Logo

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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...

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Published in: International Journal of Molecular Sciences
ISSN: 1422-0067
Published: MDPI AG 2021
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URI: https://cronfa.swan.ac.uk/Record/cronfa58729
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spelling v2 58729 2021-11-22 L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease 2cb3d1d96a7870a84d2f758e865172e6 0000-0002-4234-0033 Jeffrey Davies Jeffrey Davies true false 2021-11-22 BMS 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. Journal Article International Journal of Molecular Sciences 22 22 12346 MDPI AG 1422-0067 exendin-4, liraglutide, L-dopa, cell transplantation, neuroprotection, Parkinson Disease 16 11 2021 2021-11-16 10.3390/ijms222212346 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University Iraqi government_ PhD sponsor Grant: SF4914_ account number at Cardiff University 2023-09-13T14:59:18.0410772 2021-11-22T10:32:36.4035065 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Osama F. Elabi 1 Jeffrey Davies 0000-0002-4234-0033 2 Emma L. Lane 3 58729__21615__6d3fe3f0cffb4a508e7f8b0df4edcb66.pdf ijms-22-12346.pdf 2021-11-22T10:32:36.4034437 Output 4359322 application/pdf Version of Record true This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited true eng https://creativecommons.org/licenses/by/4.0/
title L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease
spellingShingle L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease
Jeffrey Davies
title_short L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease
title_full L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease
title_fullStr L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease
title_full_unstemmed L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease
title_sort L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease
author_id_str_mv 2cb3d1d96a7870a84d2f758e865172e6
author_id_fullname_str_mv 2cb3d1d96a7870a84d2f758e865172e6_***_Jeffrey Davies
author Jeffrey Davies
author2 Osama F. Elabi
Jeffrey Davies
Emma L. Lane
format Journal article
container_title International Journal of Molecular Sciences
container_volume 22
container_issue 22
container_start_page 12346
publishDate 2021
institution Swansea University
issn 1422-0067
doi_str_mv 10.3390/ijms222212346
publisher MDPI AG
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description 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.
published_date 2021-11-16T14:59:19Z
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