Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5737755 | Neuroscience | 2017 | 21 Pages |
Abstract
It was postulated that neuropeptide Y (NPY)-ergic system could be involved in the ischemic pathophysiology, however, the role of particular subtypes of NPY receptors (YRs) in neuroprotection against ischemia is still not well known. Therefore, we investigated the effect of NPY and YR ligands using in vitro and in vivo experimental ischemic stroke models. Our in vitro findings showed that NPY (0.5-1 μM) and specific agonists of Y2R (0.1-1 μM) and Y5R (0.5-1 μM) but not that of Y1R produced neuroprotective effects against oxygen-glucose deprivation (OGD)-induced neuronal cell death, being also effective when given 30 min after the end of OGD. The neuroprotective effects of Y2R and Y5R agonists were reversed by appropriate antagonists. Neuroprotection mediated by NPY, Y2R and Y5R agonists was accompanied by the inhibition of both OGD-induced calpain activation and glutamate release. Data from in vivo studies demonstrated that Y2R agonist (10 μg/6 μl; i.c.v.) not only diminished the infarct volume in rats subjected to transient middle cerebral artery occlusion (MCAO) but also improved selected gait parameters in CatWalk behavioral test, being also effective after delayed treatment. Moreover, we found that a Y5R agonist (10 μg/6 μl; i.c.v.) did not reduce MCAO-evoked brain damage but improved stride length, when it was given 30 min after starting the occlusion. In conclusion, our studies indicate that Y5 and especially Y2 receptors may be promising targets for neuroprotection against ischemic damage.
Keywords
YrsMCAOOGDintracerebroventriculari.c.v.GPCRsOFTCBFLDFNPY-irNPYTTCBOSTDMPSSY receptorsMCAO/RBIIE0246EBBS2,3,5-triphenyltetrazolium chlorideCa2+cAMPG-protein-coupled receptorsMTTCyclic adenosine monophosphateOpen field testmiddle cerebral artery occlusion/reperfusionmiddle cerebral artery occlusioncerebral blood flowDIVphysiological saline solutionEarle’s Balanced Salt Solutionday in vitrolactate dehydrogenaseLDHNeuroprotectionOxygen-glucose deprivationbase of supportPropidium iodideCatwalkNPY receptorsNeuropeptide Ypotassium ionCalcium ion
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Authors
Helena Domin, Åukasz Przykaza, Danuta Jantas, Ewa Kozniewska, PaweÅ M. Boguszewski, Maria ÅmiaÅowska,