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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorRabaneda-Lombarte, Neus
dc.contributor.authorSerratosa, Joan
dc.contributor.authorBove Badell, Jordi
dc.contributor.authorVila Bover, Miquel
dc.contributor.authorSaura, Josep
dc.contributor.authorSolà, Carme
dc.date.accessioned2021-11-24T09:16:03Z
dc.date.available2021-11-24T09:16:03Z
dc.date.issued2021-04-06
dc.identifier.citationRabaneda-Lombarte N, Serratosa J, Bové J, Vila M, Saura J, Solà C. The CD200R1 microglial inhibitory receptor as a therapeutic target in the MPTP model of Parkinson's disease. J Neuroinflammation. 2021 Apr 6;18:88.
dc.identifier.issn1742-2094
dc.identifier.urihttp://hdl.handle.net/11351/6592
dc.descriptionMicroglia; Neuroinflammation; Parkinson’s disease
dc.description.abstractBackground It is suggested that neuroinflammation, in which activated microglial cells play a relevant role, contributes to the development of Parkinson’s disease (PD). Consequently, the modulation of microglial activation is a potential therapeutic target to be taken into account to act against the dopaminergic neurodegeneration occurring in this neurological disorder. Several soluble and membrane-associated inhibitory mechanisms contribute to maintaining microglial cells in a quiescent/surveillant phenotype in physiological conditions. However, the presence of activated microglial cells in the brain in PD patients suggests that these mechanisms have been somehow overloaded. We focused our interest on one of the membrane-associated mechanisms, the CD200-CD200R1 ligand-receptor pair. Methods The acute MPTP experimental mouse model of PD was used to study the temporal pattern of mRNA expression of CD200 and CD200R1 in the context of MPTP-induced dopaminergic neurodegeneration and neuroinflammation. Dopaminergic damage was assessed by tyrosine hydroxylase (TH) immunoreactivity, and neuroinflammation was evaluated by the mRNA expression of inflammatory markers and IBA1 and GFAP immunohistochemistry. The effect of the modulation of the CD200-CD200R1 system on MPTP-induced damage was determined by using a CD200R1 agonist or CD200 KO mice. Results MPTP administration resulted in a progressive decrease in TH-positive fibres in the striatum and TH-positive neurons in the substantia nigra pars compacta, which were accompanied by transient astrogliosis, microgliosis and expression of pro- and anti-inflammatory markers. CD200 mRNA levels rapidly decreased in the ventral midbrain after MPTP treatment, while a transient decrease of CD200R1 mRNA expression was repeatedly observed in this brain area at earlier and later phases. By contrast, a transient increase in CD200R1 expression was observed in striatum. The administration of a CD200R1 agonist resulted in the inhibition of MPTP-induced dopaminergic neurodegeneration, while microglial cells showed signs of earlier activation in CD200-deficient mice. Conclusions Collectively, these findings provide evidence for a correlation between CD200-CD200R1 alterations, glial activation and neuronal loss. CD200R1 stimulation reduces MPTP-induced loss of dopaminergic neurons, and CD200 deficiency results in earlier microglial activation, suggesting that the potentiation of CD200R1 signalling is a possible approach to controlling neuroinflammation and neuronal death in PD.
dc.language.isoeng
dc.publisherBMC
dc.relation.ispartofseriesJournal of Neuroinflammation;18
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectParkinson, Malaltia de - Tractament
dc.subjectMicròglia - Efecte dels medicaments
dc.subject.meshMicroglia
dc.subject.mesh/drug effects
dc.subject.meshParkinson Disease
dc.subject.mesh/drug therapy
dc.titleThe CD200R1 microglial inhibitory receptor as a therapeutic target in the MPTP model of Parkinson’s disease
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1186/s12974-021-02132-z
dc.subject.decsmicroglía
dc.subject.decs/efectos de los fármacos
dc.subject.decsenfermedad de Parkinson
dc.subject.decs/farmacoterapia
dc.relation.publishversionhttps://doi.org/10.1186/s12974-021-02132-z
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Rabaneda-Lombarte N] Department of Cerebral Ischemia and Neurodegeneration, Institut d’Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas (CSIC), Institut d’Investigacions Biomèdiques August-Pi i Sunyer (IDIBAPS), Barcelona, Spain. Biochemistry and Molecular Biology Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain. [Serratosa J, Solà C] Department of Cerebral Ischemia and Neurodegeneration, Institut d’Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas (CSIC), Institut d’Investigacions Biomèdiques August-Pi i Sunyer (IDIBAPS), Barcelona, Spain. [Bové J] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBERNED, Barcelona, Spain. [Vila M] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBERNED, Barcelona, Spain. Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain. [Saura J] Biochemistry and Molecular Biology Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain
dc.identifier.pmid33823877
dc.identifier.wos000637502400001
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2013-2016/PI15%2F00033
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2013-2016/FPU13%2F05491
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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