Preconditioning afforded by restraint stress against convulsion-or ischemia-induced brain damage involves an up-regulation of adenosine A1 receptors
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1
Universidade de Coimbra, Centro de Neurociencias e Biologia Celular da, Portugal
Adenosine is a neuromodulator in the central nervous system through activation of inhibitory A1 receptors (A1R) and facilitatory A2A receptors (A2AR). Adenosine also controls neuronal damage through activation of A1R and A2AR: thus A1R constitute a hurdle for the spreading of brain damage, whereas A2AR activation exacerbates brain damage. Therefore, neuroprotective strategies mainly focus on A2AR blockade whereas prophylactic strategies could target the bolstering of A1R. Preconditioning can be viewed as one such prophylactic neuroprotective strategy: in fact, a sub-maximal noxious stimulus can limit subsequent neurodegeneration triggered by a more intense noxious stimulus through a process related to A1R. We observed that male adult rats (2 months old) subject to a 2 hours period of restraint stress displayed 24 hours later a 21-28% enhanced density of A1R in their hippocampus and cerebral cortex (evaluated by 3H-DPCPX binding and Western blot analysis). When rats were subject either to kainate (10 mg/kg, ip)-induced convulsions or focal ischemia upon distal occlusion of the middle cerebral artery, the rats subject to restraint stress 24 hours earlier displayed an extent of kainate-induced hippocampal lesion (FluoroJade-labelling 24 hours later) 64-73% lower (in CA1 and CA3 regions, n=4) than injured rats that were not previously subjected to restraint stress (control rats) and an extent of ischemia-induced cortical damage (2,3,5-triphenyltetrazolium chloride, TTC, labelling 24 hours later) similar to rats not subject to ischemia (n=8-12). Interestingly, treatment with the A1R antagonist DPCPX (1 mg/kg, ip) abrogated this ability of restraint stress to reduce subsequent neuronal damage by kainate (n=4) or abolish subsequent neuronal damage by ischemia (n=8-16). This indicates that the activation of A1R by endogenous extracellular adenosine plays a key role in stress-induced preconditioning against subsequent convulsions-induced and ischemia-induced cortical damage. Further studies are planned to determine if this stress-induced preconditioning dependent on A1R is associated with a greater efficiency of A1R, which might be due to the observed up-regulation of A1Rs and/or to enhanced levels of extracellular adenosine.
Supported by FCT.
Conference:
11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009.
Presentation Type:
Poster Presentation
Topic:
Abstracts
Citation:
Kaster
MP,
Canas
PM,
Melo
CS,
Silva
HB,
Tome
AR,
Cunha
RA and
Andrade
GM
(2009). Preconditioning afforded by restraint stress against convulsion-or ischemia-induced brain damage involves an up-regulation of adenosine A1 receptors.
Front. Neurosci.
Conference Abstract:
11th Meeting of the Portuguese Society for Neuroscience.
doi: 10.3389/conf.neuro.01.2009.11.062
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Received:
07 Aug 2009;
Published Online:
07 Aug 2009.
*
Correspondence:
Manuella P Kaster, Universidade de Coimbra, Centro de Neurociencias e Biologia Celular da, Alicante, Portugal, manu.kaster@gmail.com