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Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/62631

Title: Adenosine A(2A) receptors control neuroinflammation and consequent hippocampal neuronal dysfunction.
Author: LYNCH, MARINA ANNETTA
MILLS, KINGSTON
Sponsor: Health Research Board
Author's Homepage: http://people.tcd.ie/lynchma
http://people.tcd.ie/millsk
Keywords: neuroinflammation
Issue Date: 2011
Citation: Rebola N, Simões AP, Canas PM, Tomé AR, Andrade GM, Barry CE, Agostinho PM, Lynch MA, Cunha RA, Adenosine A(2A) receptors control neuroinflammation and consequent hippocampal neuronal dysfunction., Journal of Neurochemistry, 117, 1, 2011, 100 111
Series/Report no.: Journal of Neurochemistry
117
1
Abstract: The blockade of adenosine A2A 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-1b 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-1b 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.
Description: PUBLISHED
URI: http://hdl.handle.net/2262/62631
Related links: http://dx.doi.org/10.1111/j.1471-4159.2011.07178.x
Appears in Collections:Physiology (Scholarly Publications)

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