Dopamine receptor D3 signalling in astrocytes promotes neuroinflammation

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dc.contributor.authorMontoya, Andro
dc.contributor.authorElgueta, Daniela
dc.contributor.authorCampos, Javier
dc.contributor.authorChovar, Ornella
dc.contributor.authorFalcón, Paulina
dc.contributor.authorMatus, Soledad
dc.contributor.authorAlfaro, Iván
dc.contributor.authorBono, María Rosa
dc.contributor.authorPacheco, Rodrigo
dc.date.accessioned2021-11-08T14:14:52Z
dc.date.available2021-11-08T14:14:52Z
dc.date.issued2019-12
dc.descriptionIndexación: Scopues
dc.description.abstractBackground: Neuroinflammation constitutes a pathogenic process leading to neurodegeneration in several disorders, including Alzheimer's disease, Parkinson's disease (PD) and sepsis. Despite microglial cells being the central players in neuroinflammation, astrocytes play a key regulatory role in this process. Our previous results indicated that pharmacologic-Antagonism or genetic deficiency of dopamine receptor D3 (DRD3) attenuated neuroinflammation and neurodegeneration in two mouse models of PD. Here, we studied how DRD3-signalling affects the dynamic of activation of microglia and astrocyte in the context of systemic inflammation. Methods: Neuroinflammation was induced by intraperitoneal administration of LPS. The effect of genetic DRD3-deficiency or pharmacologic DRD3-Antagonism in the functional phenotype of astrocytes and microglia was determined by immunohistochemistry and flow cytometry at different time-points. Results: Our results show that DRD3 was expressed in astrocytes, but not in microglial cells. DRD3 deficiency resulted in unresponsiveness of astrocytes and in attenuated microglial activation upon systemic inflammation. Furthermore, similar alterations in the functional phenotypes of glial cells were observed by DRD3 antagonism and genetic deficiency of DRD3 upon LPS challenge. Mechanistic analyses show that DRD3 deficiency resulted in exacerbated expression of the anti-inflammatory protein Fizz1 in glial cells both in vitro and in vivo. Conclusions: These results suggest that DRD3 signalling regulates the dynamic of the acquisition of pro-inflammatory and anti-inflammatory features by astrocytes and microglia, finally favouring microglial activation and promoting neuroinflammation. © 2019 The Author(s).es
dc.description.urihttps://jneuroinflammation.biomedcentral.com/track/pdf/10.1186/s12974-019-1652-8.pdf
dc.identifier.citationJournal of Neuroinflammation Volume 16, Issue 16 December 2019 Article number 258es
dc.identifier.doi10.1186/s12974-019-1652-8
dc.identifier.issn17422094
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/20784
dc.language.isoenes
dc.publisherBioMed Central Ltd.es
dc.rights.licenseAtribución 4.0 Internacional (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subjectAstrocyteses
dc.subjectDopamine receptorses
dc.subjectMicrogliaes
dc.subjectNeuroinflammationes
dc.titleDopamine receptor D3 signalling in astrocytes promotes neuroinflammationes
dc.typeArtículoes
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