title: Neuroprotection by neuropeptide Y in cell and animal models of Parkinson's disease.
abstract: 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.
authors.affiliation: Institut de Physiologie et Biologie Cellulaires, Université de Poitiers, Centre National de la Recherche Scientifique (CNRS), Poitiers, France.
authors.forename: Mickael
authors.initials: M
authors.lastname: Decressac
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Pain
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Chabeauti
authors.forename: Laura
authors.initials: L
authors.lastname: Frangeul
authors.forename: Nathalie
authors.initials: N
authors.lastname: Thiriet
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.forename: Jackie
authors.initials: J
authors.lastname: Vergote
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chalon
authors.forename: Mohamed
authors.initials: M
authors.lastname: Jaber
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Gaillard
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001345:Autoradiography; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007839:Functional Laterality; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009447:Neuroblastoma / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D009478:Neuropeptide Y / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009662:Nortropanes / Q000493:pharmacokinetics; D009842:Oligopeptides / Q000627:therapeutic use; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000150:complications / Q000209:etiology / Q000517:prevention & control*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000172:deficiency; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; C092926:BIBP 3226; D050483:Dopamine Plasma Membrane Transport Proteins; D004791:Enzyme Inhibitors; C113010:N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane; D009478:Neuropeptide Y; D018696:Neuroprotective Agents; D009662:Nortropanes; D009842:Oligopeptides; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; D016627:Oxidopamine; D001120:Arginine; D014446:Tyrosine 3-Monooxygenase