{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T14:32:08Z","timestamp":1762353128063,"version":"build-2065373602"},"reference-count":84,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Iraqi government_ PhD sponsor","award":["SF4914_ account number at Cardiff University"],"award-info":[{"award-number":["SF4914_ account number at Cardiff University"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cell therapy is a promising treatment for Parkinson\u2019s 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 \u03bcg\/kg twice daily or liraglutide, 100 \u03bcg\/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.<\/jats:p>","DOI":"10.3390\/ijms222212346","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T11:32:03Z","timestamp":1637062323000},"page":"12346","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1810-2796","authenticated-orcid":false,"given":"Osama F.","family":"Elabi","sequence":"first","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4234-0033","authenticated-orcid":false,"given":"Jeffrey S.","family":"Davies","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, School of Medicine, Swansea University, Swansea SA2 8PP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma L.","family":"Lane","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1001\/jamaneurol.2017.3299","article-title":"The Parkinson Pandemic-A Call to Action","volume":"75","author":"Dorsey","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1093\/brain\/114.5.2283","article-title":"Ageing and Parkinson\u2019s disease: Substantia nigra regional selectivity","volume":"114","author":"Fearnley","year":"1991","journal-title":"Brain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1001\/jamaneurol.2013.4749","article-title":"Long-term clinical outcome of fetal cell transplantation for Parkinson disease: Two case reports","volume":"71","author":"Kefalopoulou","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7","DOI":"10.2967\/jnumed.109.066811","article-title":"Dopamine cell implantation in Parkinson\u2019s disease: Long-term clinical and (18)F-FDOPA PET outcomes","volume":"51","author":"Ma","year":"2010","journal-title":"J. Nucl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.celrep.2014.05.027","article-title":"Long-term health of dopaminergic neuron transplants in Parkinson\u2019s disease patients","volume":"7","author":"Hallett","year":"2014","journal-title":"Cell Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1056\/NEJM200103083441002","article-title":"Transplantation of embryonic dopamine neurons for severe Parkinson\u2019s disease","volume":"344","author":"Freed","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/ana.10720","article-title":"A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson\u2019s disease","volume":"54","author":"Olanow","year":"2003","journal-title":"Ann. Neurol."},{"key":"ref_8","unstructured":"TRANSEURO (2021, September 20). Innovative Approach for the Treatment of Parkinson\u2019s Disease. Available online: https:\/\/transeuro.org.uk."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/bs.pbr.2016.11.011","article-title":"Strategies for bringing stem cell-derived dopamine neurons to the clinic: A European approach (STEM-PD)","volume":"230","author":"Kirkeby","year":"2017","journal-title":"Prog. Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1038\/s41591-019-0507-2","article-title":"Designing stem-cell-based dopamine cell replacement trials for Parkinson\u2019s disease","volume":"25","author":"Barker","year":"2019","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/S0166-2236(96)80038-5","article-title":"Fetal nigral transplantation as a therapy for Parkinson\u2019s disease","volume":"19","author":"Olanow","year":"1996","journal-title":"Trends Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/mds.870130303","article-title":"Fetal nigral grafts survive and mediate clinical benefit in a patient with Parkinson\u2019s disease","volume":"13","author":"Kordower","year":"1998","journal-title":"Mov. Disord."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1177\/096368970000900205","article-title":"Improving the survival of grafted dopaminergic neurons: A review over current approaches","volume":"9","author":"Brundin","year":"2000","journal-title":"Cell Transpl."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/4785","article-title":"Caspase inhibition reduces apoptosis and increases survival of nigral transplants","volume":"5","author":"Schierle","year":"1999","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"NS20210028","DOI":"10.1042\/NS20210028","article-title":"Anti-inflammatory cytokine-eluting collagen hydrogel reduces the host immune response to dopaminergic cell transplants in a rat model of Parkinson\u2019s disease","volume":"5","author":"Cabre","year":"2021","journal-title":"Neuronal Signal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16033","DOI":"10.1038\/s41598-017-15970-w","article-title":"Encapsulation of primary dopaminergic neurons in a GDNF-loaded collagen hydrogel increases their survival, re-innervation and function after intra-striatal transplantation","volume":"7","author":"Moriarty","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/0361-9230(96)00001-9","article-title":"The lazaroid U-83836E improves the survival of rat embryonic mesencephalic tissue stored at 4 degrees C and subsequently used for cultures or intracerebral transplantation","volume":"39","author":"Nakao","year":"1996","journal-title":"Brain Res. Bull."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1056\/NEJM199205143262003","article-title":"Antidiabetogenic effect of glucagon-like peptide-1 (7-36)amide in normal subjects and patients with diabetes mellitus","volume":"326","author":"Gutniak","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.2337\/diacare.17.9.1039","article-title":"Subcutaneous injection of the incretin hormone glucagon-like peptide 1 abolishes postprandial glycemia in NIDDM","volume":"17","author":"Gutniak","year":"1994","journal-title":"Diabetes Care"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Augestad, I.L., Dekens, D., Karampatsi, D., Elabi, O., Zabala, A., Pintana, H., Larsson, M., Nystrom, T., Paul, G., and Darsalia, V. (2021). Normalisation of glucose metabolism by Exendin-4 in the chronic phase after stroke promotes functional recovery in male diabetic mice. Br. J. Pharmacol.","DOI":"10.21203\/rs.3.rs-210113\/v1"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"106715","DOI":"10.1016\/j.intimp.2020.106715","article-title":"Glucagon-like peptide-1 receptor agonist Exendin-4 improves neurological outcomes by attenuating TBI- induced inflammatory responses and MAPK activation in rats","volume":"86","author":"Zhang","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2015.09.035","article-title":"A novel dual GLP-1 and GIP receptor agonist is neuroprotective in the MPTP mouse model of Parkinson\u2019s disease by increasing expression of BNDF","volume":"1634","author":"Ji","year":"2016","journal-title":"Brain Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3233\/JPD-140364","article-title":"Motor and cognitive advantages persist 12 months after exenatide exposure in Parkinson\u2019s disease","volume":"4","author":"Dickson","year":"2014","journal-title":"J. Parkinsons Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1742-2094-5-19","article-title":"Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson\u2019s disease","volume":"5","author":"Harkavyi","year":"2008","journal-title":"J. Neuroinflamm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1677\/JOE-09-0132","article-title":"Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson\u2019s disease","volume":"202","author":"Kim","year":"2009","journal-title":"J. Endocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1016\/S0140-6736(17)31585-4","article-title":"Exenatide once weekly versus placebo in Parkinson\u2019s disease: A randomised, double-blind, placebo-controlled trial","volume":"390","author":"Athauda","year":"2017","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/bs.pbr.2019.10.008","article-title":"Repurposing anti-diabetic drugs for the treatment of Parkinson\u2019s disease: Rationale and clinical experience","volume":"252","author":"Foltynie","year":"2020","journal-title":"Prog. Brain Res."},{"key":"ref_28","first-page":"407152","article-title":"Neuroprotection by Exendin-4 Is GLP-1 Receptor Specific but DA D3 Receptor Dependent, Causing Altered BrdU Incorporation in Subventricular Zone and Substantia Nigra","volume":"2013","author":"Harkavyi","year":"2013","journal-title":"J. Neurodegener. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3233\/JPD-181503","article-title":"Semaglutide is Neuroprotective and Reduces alpha-Synuclein Levels in the Chronic MPTP Mouse Model of Parkinson\u2019s Disease","volume":"9","author":"Zhang","year":"2019","journal-title":"J. Parkinsons Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1111\/j.1471-4159.2010.06731.x","article-title":"Enhancing the GLP-1 receptor signaling pathway leads to proliferation and neuroprotection in human neuroblastoma cells","volume":"113","author":"Li","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1093\/brain\/123.7.1365","article-title":"Embryonic ventral mesencephalic grafts improve levodopa-induced dyskinesia in a rat model of Parkinson\u2019s disease","volume":"123","author":"Lee","year":"2000","journal-title":"Brain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.nbd.2005.11.011","article-title":"The impact of graft size on the development of dyskinesia following intrastriatal grafting of embryonic dopamine neurons in the rat","volume":"22","author":"Lane","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.neuropharm.2012.06.011","article-title":"Pharmacological modulation of amphetamine-induced dyskinesia in transplanted hemi-parkinsonian rats","volume":"63","author":"Smith","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1172\/JCI59903","article-title":"Demonstrated brain insulin resistance in Alzheimer\u2019s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline","volume":"122","author":"Talbot","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8141","DOI":"10.1523\/JNEUROSCI.1607-04.2004","article-title":"Glucagon-like peptide 1 excites hypocretin\/orexin neurons by direct and indirect mechanisms: Implications for viscera-mediated arousal","volume":"24","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1073\/pnas.0806720106","article-title":"GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism","volume":"106","author":"Li","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1097\/WNR.0b013e32832fbf14","article-title":"Receptors for the incretin glucagon-like peptide-1 are expressed on neurons in the central nervous system","volume":"20","author":"Hamilton","year":"2009","journal-title":"NeuroReport"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1111\/j.1476-5381.2012.02100.x","article-title":"Exendin-4 reverts behavioural and neurochemical dysfunction in a pre-motor rodent model of Parkinson\u2019s disease with noradrenergic deficit","volume":"167","author":"Rampersaud","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1111\/ejn.14096","article-title":"Post hoc analysis of the Exenatide-PD trial-Factors that predict response","volume":"49","author":"Athauda","year":"2019","journal-title":"Eur. J. Neurosci."},{"key":"ref_40","first-page":"979","article-title":"Glial cell line-derived neurotrophic factor increases survival, growth and function of intrastriatal fetal nigral dopaminergic grafts","volume":"75","author":"Rosenblad","year":"1996","journal-title":"Neuroscience"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nm0195-53","article-title":"Basic fibroblast growth factor increases dopaminergic graft survival and function in a rat model of Parkinson\u2019s disease","volume":"1","author":"Takayama","year":"1995","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/S0006-8993(99)01176-2","article-title":"Effects of anaesthetics and lazaroid U-83836E on survival of transplanted rat dopaminergic neurones","volume":"821","author":"Karlsson","year":"1999","journal-title":"Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s10787-017-0331-6","article-title":"Sitagliptin and liraglutide reversed nigrostriatal degeneration of rodent brain in rotenone-induced Parkinson\u2019s disease","volume":"25","author":"Badawi","year":"2017","journal-title":"Inflammopharmacology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.brainres.2016.05.038","article-title":"Characterization of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in rat partial and full nigral 6-hydroxydopamine lesion models of Parkinson\u2019s disease","volume":"1646","author":"Hansen","year":"2016","journal-title":"Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ejphar.2017.06.029","article-title":"A novel GLP-1\/GIP dual agonist is more effective than liraglutide in reducing inflammation and enhancing GDNF release in the MPTP mouse model of Parkinson\u2019s disease","volume":"812","author":"Yuan","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1093\/jnen\/60.8.741","article-title":"Cell survival and clinical outcome following intrastriatal transplantation in Parkinson disease","volume":"60","author":"Hagell","year":"2001","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/cne.22035","article-title":"Pattern of long-term sensorimotor recovery following intrastriatal and--accumbens DA micrografts in a rat model of Parkinson\u2019s disease","volume":"515","author":"Falkenstein","year":"2009","journal-title":"J. Comp. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.bbi.2016.11.014","article-title":"Influence of chronic L-DOPA treatment on immune response following allogeneic and xenogeneic graft in a rat model of Parkinson\u2019s disease","volume":"61","author":"Breger","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1002\/syn.21941","article-title":"l-DOPA-induced dyskinesia in Parkinson\u2019s disease: Are neuroinflammation and astrocytes key elements?","volume":"70","author":"Bortolanza","year":"2016","journal-title":"Synapse"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Brabazon, F., Bermudez, S., Shaughness, M., Khayrullina, G., and Byrnes, K.R. (2018). The effects of insulin on the inflammatory activity of BV2 microglia. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201878"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1186\/1742-2094-9-276","article-title":"GLP-1 secretion by microglial cells and decreased CNS expression in obesity","volume":"9","author":"Kappe","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1186\/s12974-021-02218-8","article-title":"High-fat diet-induced diabetes leads to vascular alterations, pericyte reduction, and perivascular depletion of microglia in a 6-OHDA toxin model of Parkinson disease","volume":"18","author":"Elabi","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.expneurol.2013.11.001","article-title":"Metabolic inflammation exacerbates dopaminergic neuronal degeneration in response to acute MPTP challenge in type 2 diabetes mice","volume":"251","author":"Wang","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1002\/mds.28124","article-title":"Diabetes Causes Dysfunctional Dopamine Neurotransmission Favoring Nigrostriatal Degeneration in Mice","volume":"35","author":"Alberquilla","year":"2020","journal-title":"Mov. Disord."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e1654","DOI":"10.1212\/WNL.0000000000005475","article-title":"Diabetes mellitus and Parkinson disease","volume":"90","author":"Pagano","year":"2018","journal-title":"Neurology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1002\/mds.28551","article-title":"Type 2 Diabetes as a Determinant of Parkinson\u2019s Disease Risk and Progression","volume":"36","author":"Chohan","year":"2021","journal-title":"Mov. Disord."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"302","DOI":"10.3389\/fnagi.2019.00302","article-title":"Diabetes, a Contemporary Risk for Parkinson\u2019s Disease: Epidemiological and Cellular Evidences","volume":"11","author":"Sergi","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/0006-8993(95)00260-W","article-title":"Allogeneic grafts of fetal dopamine neurons: Immunological reactions following active and adoptive immunizations","volume":"680","author":"Shinoda","year":"1995","journal-title":"Brain Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/0304-3940(94)90597-5","article-title":"Allogeneic grafts of fetal dopamine neurons: Behavioral indices of immunological interactions","volume":"171","author":"Hudson","year":"1994","journal-title":"Neurosci. Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.2337\/db13-1954","article-title":"Inflammation, defective insulin signaling, and mitochondrial dysfunction as common molecular denominators connecting type 2 diabetes to Alzheimer disease","volume":"63","author":"Ferreira","year":"2014","journal-title":"Diabetes"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/S0165-5728(03)00270-4","article-title":"The enhancement of T cell proliferation by L-dopa is mediated peripherally and does not involve interleukin-2","volume":"142","author":"Carr","year":"2003","journal-title":"J. Neuroimmunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jdermsci.2013.03.008","article-title":"D1-like dopamine receptors antagonist inhibits cutaneous immune reactions mediated by Th2 and mast cells","volume":"71","author":"Mori","year":"2013","journal-title":"J. Dermatol. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.bbrc.2012.07.086","article-title":"Glucagon-like peptide-1 (GLP-1) induces M2 polarization of human macrophages via STAT3 activation","volume":"425","author":"Shiraishi","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1111\/j.2042-7158.2011.01394.x","article-title":"Exendin-4 treatment enhances L-DOPA evoked release of striatal dopamine and decreases dyskinetic movements in the 6-hydoxydopamine lesioned rat","volume":"64","author":"Abuirmeileh","year":"2012","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"785","DOI":"10.3389\/fnins.2020.00785","article-title":"PT320, Sustained-Release Exendin-4, Mitigates L-DOPA-Induced Dyskinesia in a Rat 6-Hydroxydopamine Model of Parkinson\u2019s Disease","volume":"14","author":"Yu","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/s41591-018-0051-5","article-title":"Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson\u2019s disease","volume":"24","author":"Yun","year":"2018","journal-title":"Nat. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1007\/s13311-021-01018-5","article-title":"Neuroprotection of Exendin-4 by Enhanced Autophagy in a Parkinsonian Rat Model of alpha-Synucleinopathy","volume":"18","author":"Bu","year":"2021","journal-title":"Neurotherapeutics"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"113693","DOI":"10.1016\/j.expneurol.2021.113693","article-title":"An extended release GLP-1 analogue increases alpha-synuclein accumulation in a mouse model of prodromal Parkinson\u2019s disease","volume":"341","author":"Bergkvist","year":"2021","journal-title":"Exp. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6544","DOI":"10.1073\/pnas.1605245113","article-title":"Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain","volume":"113","author":"Li","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/ana.24820","article-title":"Robust graft survival and normalized dopaminergic innervation do not obligate recovery in a Parkinson disease patient","volume":"81","author":"Kordower","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jneumeth.2011.06.012","article-title":"Increased efficacy of the 6-hydroxydopamine lesion of the median forebrain bundle in small rats, by modification of the stereotaxic coordinates","volume":"200","author":"Torres","year":"2011","journal-title":"J. Neurosci. Methods"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0014-2999(68)90164-7","article-title":"6-Hydroxy-dopamine induced degeneration of central monoamine neurons","volume":"5","author":"Ungerstedt","year":"1968","journal-title":"Eur. J. Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Dunnett, S.B., Boulton, A.A., and Baker, G.B. (2000). Dissecting Embryonic Neural Tissues for Transplantation. Neural Transplantation Methods, Humana Press.","DOI":"10.1007\/978-1-59259-690-4"},{"key":"ref_74","first-page":"1","article-title":"Intracerebral grafting of neuronal cell suspensions. I. Introduction and general methods of preparation","volume":"522","author":"Bjorklund","year":"1983","journal-title":"Acta Physiol. Scand. Suppl."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1016\/j.neuroscience.2007.03.037","article-title":"Improved survival of young donor age dopamine grafts in a rat model of Parkinson\u2019s disease","volume":"146","author":"Torres","year":"2007","journal-title":"Neuroscience"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.ejphar.2009.12.023","article-title":"Glucagon-like peptide-1 analogues enhance synaptic plasticity in the brain: A link between diabetes and Alzheimer\u2019s disease","volume":"630","author":"McClean","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/0006-8993(70)90187-3","article-title":"Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system","volume":"24","author":"Ungerstedt","year":"1970","journal-title":"Brain Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1006\/exnr.1998.6848","article-title":"Characterization of behavioral and neurodegenerative changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat","volume":"152","author":"Kirik","year":"1998","journal-title":"Exp. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/S0028-3908(00)00005-8","article-title":"CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury","volume":"39","author":"Schallert","year":"2000","journal-title":"Neuropharmacology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1006\/nbdi.2002.0499","article-title":"L-DOPA-induced dyskinesia in the intrastriatal 6-hydroxydopamine model of parkinson\u2019s disease: Relation to motor and cellular parameters of nigrostriatal function","volume":"10","author":"Winkler","year":"2002","journal-title":"Neurobiol. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.nbd.2012.10.013","article-title":"Comparison of rating scales used to evaluate L-DOPA-induced dyskinesia in the 6-OHDA lesioned rat","volume":"50","author":"Breger","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_82","unstructured":"MILLIPLEX\u00ae MAP (2021, September 20). Rat Metabolic Magnetic Bead Panel Kit 96 Well Plate Assay. Available online: https:\/\/filgen.jp\/Product\/Bioscience19-Bioplex\/RMHMAG-84K.MPX.pdf."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/(SICI)1097-0185(199803)250:3<373::AID-AR12>3.0.CO;2-L","article-title":"What was wrong with the Abercrombie and empirical cell counting methods? A review","volume":"250","author":"Hedreen","year":"1998","journal-title":"Anat. Rec."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/22\/12346\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:30:49Z","timestamp":1760167849000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/22\/12346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,16]]},"references-count":84,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222212346"],"URL":"https:\/\/doi.org\/10.3390\/ijms222212346","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,11,16]]}}}