کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6021411 | 1580634 | 2016 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Genetic and pharmacological evidence that endogenous nociceptin/orphanin FQ contributes to dopamine cell loss in Parkinson's disease
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کلمات کلیدی
MPTP1-methyl-4-phenyl-1,2,5,6-tetrahydropyridineSubstantia nigra reticulataNOP6-OHDASNRSNC6-HydroxydopamineMPP+ - MPP +N/OFQ - N / OFQnociceptin/orphanin FQ - nociceptin / orphanin FQα-synuclein - α-سینوکلینParkinson's disease - بیماری پارکینسونtyrosine hydroxylase - تیروزین هیدروکسیلازDopamine - دوپامینphosphorylated α-synuclein - فسفریکیلاسیون α-سینوکلینSubstantia nigra compacta - متراکم توده سیاهNeuroprotection - محافظت نورونی یا محافظت از عصبNOP receptor - گیرنده NOP
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
To investigate whether the endogenous neuropeptide nociceptin/orphanin FQ (N/OFQ) contributes to the death of dopamine neurons in Parkinson's disease, we undertook a genetic and a pharmacological approach using NOP receptor knockout (NOPâ/â) mice, and the selective and potent small molecule NOP receptor antagonist (â)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol (SB-612111). Stereological unbiased methods were used to estimate the total number of dopamine neurons in the substantia nigra of i) NOPâ/â mice acutely treated with the parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), ii) naïve mice subacutely treated with MPTP, alone or in combination with SB-612111, iii) rats injected with a recombinant adeno-associated viral (AAV) vector overexpressing human mutant p.A53T α-synuclein, treated with vehicle or SB-612111. NOPâ/â mice showed a 50% greater amount of nigral dopamine neurons spared in response to acute MPTP compared to controls, which was associated with a milder motor impairment. SB-612111, given 4 days after MPTP treatment to mimic the clinical condition, prevented the loss of nigral dopamine neurons and striatal dopaminergic terminals caused by subacute MPTP. SB-612111, administered a week after the AAV injections in a clinically-driven protocol, also increased by 50% both the number of spared nigral dopamine neurons and striatal dopamine terminals, and prevented accompanying motor deficits induced by α-synuclein. We conclude that endogenous N/OFQ contributes to dopamine neuron loss in pathogenic and etiologic models of Parkinson's disease through NOP receptor-mediated mechanisms. NOP receptor antagonists might prove effective as disease-modifying agents in Parkinson's disease, through the rescue of degenerating nigral dopamine neurons and/or the protection of the healthy ones.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 89, May 2016, Pages 55-64
Journal: Neurobiology of Disease - Volume 89, May 2016, Pages 55-64
نویسندگان
Ludovico Arcuri, Riccardo Viaro, Simone Bido, Francesco Longo, Mariangela Calcagno, Pierre-Olivier Fernagut, Nurulain T. Zaveri, Girolamo Calò, Erwan Bezard, Michele Morari,