期刊
NEUROBIOLOGY OF AGING
卷 33, 期 9, 页码 2125-2137出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2011.06.018
关键词
Parkinson's disease; Neuropeptide Y; Neuroprotection
资金
- CNRS Longevite et Vieillissement
- University of Poitiers
- Fondation de France
- Region Poitou-Charentes
- CPER
- FEDER programs
This study was aimed to investigate the potential neuroprotective effect of neuropeptide Y (NPY) on the survival of dopaminergic cells in both in vitro and in animal models of Parkinson's disease (PD). NPY protected human SH-SY5Y dopaminergic neuroblastoma cells from 6-hydroxydopamine-induced toxicity. In rat and mice models of PD, striatal injection of NPY preserved the nigrostriatal dopamine pathway from degeneration as evidenced by quantification of (1) tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta, levels of (2) striatal tyrosine hydroxylase and dopamine transporter, (3) dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) as well as (4) rotational behavior. NPY had no neuroprotective effects in mice treated with Y 2 receptor antagonist or in transgenic mice deficient for Y 2 receptor suggesting that NPY effects are mediated through this receptor. Stimulation of Y 2 receptor by NPY triggered the activation of both the ERK1/2 and Akt pathways but did not modify levels of brain derived neurotrophic factor (BDNF) or glial cell line-derived neurotrophic factor. These results open new perspectives in neuroprotective therapies using NPY and suggest potential beneficial effects in PD. (C) 2012 Elsevier Inc. All rights reserved.
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