Montoya, AndroElgueta, DanielaCampos, JavierChovar, OrnellaFalcón, PaulinaMatus, SoledadAlfaro, IvánBono, María RosaPacheco, Rodrigo2021-11-082021-11-082019-12Journal of Neuroinflammation Volume 16, Issue 16 December 2019 Article number 25817422094http://repositorio.unab.cl/xmlui/handle/ria/20784Indexación: ScopuBackground: 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).enAstrocytesDopamine receptorsMicrogliaNeuroinflammationArtículoAtribución 4.0 Internacional (CC BY 4.0)10.1186/s12974-019-1652-8