Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A<sub>2A</sub> receptor-dependent manner: A<sub>2A</sub> receptor blockade prevents BDNF release and proliferation of microglia
<p>Abstract</p> <p>Background</p> <p>Brain-derived neurotrophic factor (BDNF) has been shown to control microglial responses in neuropathic pain. Since adenosine A<sub>2A</sub> receptors (A<sub>2A</sub>Rs) control neuroinflammation, as well as th...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2013-01-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://www.jneuroinflammation.com/content/10/1/16 |
| _version_ | 1818144689949245440 |
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| author | Gomes Catarina Ferreira Raquel George Jimmy Sanches Rui Rodrigues Diana I Gonçalves Nélio Cunha Rodrigo A |
| author_facet | Gomes Catarina Ferreira Raquel George Jimmy Sanches Rui Rodrigues Diana I Gonçalves Nélio Cunha Rodrigo A |
| author_sort | Gomes Catarina |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Brain-derived neurotrophic factor (BDNF) has been shown to control microglial responses in neuropathic pain. Since adenosine A<sub>2A</sub> receptors (A<sub>2A</sub>Rs) control neuroinflammation, as well as the production and function of BDNF, we tested to see if A<sub>2A</sub>R controls the microglia-dependent secretion of BDNF and the proliferation of microglial cells, a crucial event in neuroinflammation.</p> <p>Methods</p> <p>Murine N9 microglial cells were challenged with lipopolysaccharide (LPS, 100 ng/mL) in the absence or in the presence of the A<sub>2A</sub>R antagonist, SCH58261 (50 nM), as well as other modulators of A<sub>2A</sub>R signaling. The BDNF cellular content and secretion were quantified by Western blotting and ELISA, A<sub>2A</sub>R density was probed by Western blotting and immunocytochemistry and cell proliferation was assessed by BrdU incorporation. Additionally, the A<sub>2A</sub>R modulation of LPS-driven cell proliferation was also tested in primary cultures of mouse microglia.</p> <p>Results</p> <p>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<sub>2A</sub>R density. Notably, removing endogenous extracellular adenosine or blocking A<sub>2A</sub>R prevented the LPS-mediated increase of both BDNF secretion and proliferation, as well as exogenous BDNF-induced proliferation.</p> <p>Conclusions</p> <p>We conclude that A<sub>2A</sub>R activation plays a mandatory role controlling the release of BDNF from activated microglia, as well as the autocrine/paracrine proliferative role of BDNF.</p> |
| first_indexed | 2024-12-11T11:51:34Z |
| format | Article |
| id | doaj.art-fe73585751d545fa9a7d06e6e071635e |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-11T11:51:34Z |
| publishDate | 2013-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-fe73585751d545fa9a7d06e6e071635e2022-12-22T01:08:21ZengBMCJournal of Neuroinflammation1742-20942013-01-011011610.1186/1742-2094-10-16Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A<sub>2A</sub> receptor-dependent manner: A<sub>2A</sub> receptor blockade prevents BDNF release and proliferation of microgliaGomes CatarinaFerreira RaquelGeorge JimmySanches RuiRodrigues Diana IGonçalves NélioCunha Rodrigo A<p>Abstract</p> <p>Background</p> <p>Brain-derived neurotrophic factor (BDNF) has been shown to control microglial responses in neuropathic pain. Since adenosine A<sub>2A</sub> receptors (A<sub>2A</sub>Rs) control neuroinflammation, as well as the production and function of BDNF, we tested to see if A<sub>2A</sub>R controls the microglia-dependent secretion of BDNF and the proliferation of microglial cells, a crucial event in neuroinflammation.</p> <p>Methods</p> <p>Murine N9 microglial cells were challenged with lipopolysaccharide (LPS, 100 ng/mL) in the absence or in the presence of the A<sub>2A</sub>R antagonist, SCH58261 (50 nM), as well as other modulators of A<sub>2A</sub>R signaling. The BDNF cellular content and secretion were quantified by Western blotting and ELISA, A<sub>2A</sub>R density was probed by Western blotting and immunocytochemistry and cell proliferation was assessed by BrdU incorporation. Additionally, the A<sub>2A</sub>R modulation of LPS-driven cell proliferation was also tested in primary cultures of mouse microglia.</p> <p>Results</p> <p>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<sub>2A</sub>R density. Notably, removing endogenous extracellular adenosine or blocking A<sub>2A</sub>R prevented the LPS-mediated increase of both BDNF secretion and proliferation, as well as exogenous BDNF-induced proliferation.</p> <p>Conclusions</p> <p>We conclude that A<sub>2A</sub>R activation plays a mandatory role controlling the release of BDNF from activated microglia, as well as the autocrine/paracrine proliferative role of BDNF.</p>http://www.jneuroinflammation.com/content/10/1/16Adenosine A<sub>2A</sub> receptorsNeuroinflammationMicrogliaBDNF |
| spellingShingle | Gomes Catarina Ferreira Raquel George Jimmy Sanches Rui Rodrigues Diana I Gonçalves Nélio Cunha Rodrigo A Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A<sub>2A</sub> receptor-dependent manner: A<sub>2A</sub> receptor blockade prevents BDNF release and proliferation of microglia Journal of Neuroinflammation Adenosine A<sub>2A</sub> receptors Neuroinflammation Microglia BDNF |
| title | Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A<sub>2A</sub> receptor-dependent manner: A<sub>2A</sub> receptor blockade prevents BDNF release and proliferation of microglia |
| title_full | Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A<sub>2A</sub> receptor-dependent manner: A<sub>2A</sub> receptor blockade prevents BDNF release and proliferation of microglia |
| title_fullStr | Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A<sub>2A</sub> receptor-dependent manner: A<sub>2A</sub> receptor blockade prevents BDNF release and proliferation of microglia |
| title_full_unstemmed | Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A<sub>2A</sub> receptor-dependent manner: A<sub>2A</sub> receptor blockade prevents BDNF release and proliferation of microglia |
| title_short | Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A<sub>2A</sub> receptor-dependent manner: A<sub>2A</sub> receptor blockade prevents BDNF release and proliferation of microglia |
| title_sort | activation of microglial cells triggers a release of brain derived neurotrophic factor bdnf inducing their proliferation in an adenosine a sub 2a sub receptor dependent manner a sub 2a sub receptor blockade prevents bdnf release and proliferation of microglia |
| topic | Adenosine A<sub>2A</sub> receptors Neuroinflammation Microglia BDNF |
| url | http://www.jneuroinflammation.com/content/10/1/16 |
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