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Neuroscience. 2017 Mar 6;344:305-325. doi: 10.1016/j.neuroscience.2016.12.040. Epub 2017 Jan 3.

Neuropeptide Y Y2 and Y5 receptors as promising targets for neuroprotection in primary neurons exposed to oxygen-glucose deprivation and in transient focal cerebral ischemia in rats.

Author information

1
Institute of Pharmacology, Polish Academy of Sciences, Department of Neurobiology, 31-343 Kraków, Smętna Street 12, Poland. Electronic address: domin@if-pan.krakow.pl.
2
Mossakowski Medical Research Centre, Polish Academy of Sciences, Department of Neurosurgery, Laboratory of Experimental Neurosurgery, Pawińskiego Street 5, 02-106 Warsaw, Poland.
3
Institute of Pharmacology, Polish Academy of Sciences, Department of Experimental Neuroendocrinology, 31-343 Kraków, Smętna Street 12, Poland.
4
Mossakowski Medical Research Centre, Polish Academy of Sciences, Department of Neurosurgery, Laboratory of Experimental Neurosurgery, Pawińskiego Street 5, 02-106 Warsaw, Poland; Medical University of Warsaw, Department of Experimental and Clinical Physiology, Pawińskiego Street 3C, 02-106 Warsaw, Poland.
5
Laboratory of Animal Models, Neurobiology Centre, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland.
6
Institute of Pharmacology, Polish Academy of Sciences, Department of Neurobiology, 31-343 Kraków, Smętna Street 12, Poland.

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 (0.5-1μM) and specific agonists of Y2R (0.1-1μM) and Y5R (0.5-1μM) but not that of Y1R produced neuroprotective effects against oxygen-glucose deprivation (OGD)-induced neuronal cell death, being also effective when given 30min 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 (10μg/6μl; 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 (10μg/6μl; i.c.v.) did not reduce MCAO-evoked brain damage but improved stride length, when it was given 30min 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:

CatWalk; MCAO; NPY; OGD; Y receptors; neuroprotection

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