Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A2A receptor-dependent manner: A2A receptor blockade prevents BDNF release and proliferation of microglia

Journal of Neuroinflammation

Rodrigo A Cunha¹  Nélio Gonçalves²  Diana I Rodrigues³  Rui Sanches³  Jimmy George³  Raquel Ferreira³  Catarina Gomes³ 

[1] FMUC - Faculty of Medicine, University of Coimbra, Coimbra, 3004-504, Portugal;Faculty of Pharmacy, University of Coimbra, Coimbra, 3000-548, Portugal;Center for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, Coimbra, 3004-517, Portugal

关键词: BDNF;    Microglia;    Neuroinflammation;    Adenosine A_2A receptors;   

Others  :  1160047
DOI  :  10.1186/1742-2094-10-16

 received in 2012-03-07, accepted in 2013-01-18,  发布年份 2013

【 摘 要 】

Background

Brain-derived neurotrophic factor (BDNF) has been shown to control microglial responses in neuropathic pain. Since adenosine A_2A receptors (A_2ARs) control neuroinflammation, as well as the production and function of BDNF, we tested to see if A_2AR controls the microglia-dependent secretion of BDNF and the proliferation of microglial cells, a crucial event in neuroinflammation.

Methods

Murine N9 microglial cells were challenged with lipopolysaccharide (LPS, 100 ng/mL) in the absence or in the presence of the A_2AR antagonist, SCH58261 (50 nM), as well as other modulators of A_2AR signaling. The BDNF cellular content and secretion were quantified by Western blotting and ELISA, A_2AR density was probed by Western blotting and immunocytochemistry and cell proliferation was assessed by BrdU incorporation. Additionally, the A_2AR modulation of LPS-driven cell proliferation was also tested in primary cultures of mouse microglia.

Results

LPS induced time-dependent changes of the intra- and extracellular levels of BDNF and increased microglial proliferation. The maximal LPS-induced BDNF release was time-coincident with an LPS-induced increase of the A_2AR density. Notably, removing endogenous extracellular adenosine or blocking A_2AR prevented the LPS-mediated increase of both BDNF secretion and proliferation, as well as exogenous BDNF-induced proliferation.

Conclusions

We conclude that A_2AR activation plays a mandatory role controlling the release of BDNF from activated microglia, as well as the autocrine/paracrine proliferative role of BDNF.

【 授权许可】

   
2013 Gomes et al.; licensee BioMed Central Ltd.

【 图 表 】

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