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Adenosine A 2A receptors control neuroinflammation and consequent hippocampal neuronal dysfunction
Author(s) -
Rebola Nelson,
Simões Ana Patrícia,
Canas Paula M.,
Tomé Angelo R.,
Andrade Geanne M.,
Barry Claire E.,
Agostinho Paula M.,
Lynch Marina A.,
Cunha Rodrigo A.
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07178.x
Subject(s) - neuroinflammation , neuroprotection , adenosine a2a receptor , long term potentiation , microglia , hippocampus , neuroscience , pharmacology , inflammation , medicine , receptor , adenosine receptor , biology , agonist
J. Neurochem. (2011) 117 , 100–111. Abstract The blockade of adenosine A 2A receptors (A2AR) affords a robust neuroprotection in different noxious brain conditions. However, the mechanisms underlying this general neuroprotection are unknown. One possible mechanism could be the control of neuroinflammation that is associated with brain damage, especially because A2AR efficiently control peripheral inflammation. Thus, we tested if the intracerebroventricular injection of a selective A2AR antagonist (SCH58261) would attenuate the changes in the hippocampus triggered by intraperitoneal administration of lipopolysaccharide (LPS) that induces neuroinflammation through microglia activation. LPS administration triggers an increase in inflammatory mediators like interleukin‐1β that causes biochemical changes (p38 and c‐jun N‐terminal kinase phosphorylation and caspase 3 activation) contributing to neuronal dysfunction typified by decreased long‐term potentiation, a form of synaptic plasticity. Long‐term potentiation, measured 30 min after the tetanus, was significantly lower in LPS‐treated rats compared with control‐treated rats, while SCH58261 attenuated the LPS‐induced change. The LPS‐induced increases in phosphorylation of c‐jun N‐terminal kinase and p38 and activation of caspase 3 were also prevented by SCH58261. Significantly, SCH58261 also prevented the LPS‐induced recruitment of activated microglial cells and the increase in interleukin‐1β concentration in the hippocampus, indicating that A2AR activation is a pivotal step in mediating the neuroinflammation triggered by LPS. These results indicate that A2AR antagonists prevent neuroinflammation and support the hypothesis that this mechanism might contribute for the ability of A2AR antagonists to control different neurodegenerative diseases known to involve neuroinflammation.