Nociceptin/orphanin FQ inhibits the survival and axon growth of midbrain dopaminergic neurons through a p38-MAPK dependent mechanism

Collins, Louise M., Dal Bo, Giorgia, Calcagno, Mariangela , Monzón-Sandoval, Jimena, Sullivan, Aideen M., Gutierrez, Humberto, Morari, Michele and O’Keeffe, Gerard W. (2016) Nociceptin/orphanin FQ inhibits the survival and axon growth of midbrain dopaminergic neurons through a p38-MAPK dependent mechanism. Molecular Neurobiology, 53 (10). pp. 7284-7297. ISSN 0893-7648

Full content URL: http://doi.org/10.1007/s12035-015-9611-6

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Item Type:Article
Item Status:Live Archive

Abstract

Nociceptin/orphanin FQ (N/OFQ) is an opioid-like neuropeptide that binds and signals through a G-protein-coupled receptor called the N/OFQ peptide (NOP) receptor. N/OFQ and the NOP receptor are expressed in the midbrain and have been implicated in the pathogenesis of Parkinson’s disease (PD). Genetic removal of the N/OFQ precursor partially protects midbrain dopaminergic neurons from 1-methyl-4-phenylpyridine-induced toxicity, suggesting that endogenous N/OFQ may be detrimental to dopaminergic neurons. However, whether N/OFQ directly affects the survival and growth of dopaminergic neurons is unknown. Here, we show that N/OFQ has a detrimental effect on the survival of dopaminergic neurons and the growth of their axons in primary cultures of the E14 rat ventral mesencephalon. N/OFQ potentiates the effects of the neurotoxins 6-hydroxydopamine and 1-methyl-4-phenylpyridinium through p38-MAPK signalling. We also show that like α-synuclein, there is a significant reduction in N/OFQ messenger RNA (mRNA) expression in the midbrain of patients with Parkinson’s disease. These results demonstrate for the first time that N/OFQ is detrimental to the survival and growth of dopaminergic neurons and that its expression is altered in the midbrain of patients with Parkinson’s disease.

Keywords:Nociceptin/orphanin FQ, Parkinson’s disease, Dopaminergic, Neuron survival, Axon growth, p38-MAPK, Human, NotOAChecked
Subjects:C Biological Sciences > C700 Molecular Biology, Biophysics and Biochemistry
Divisions:College of Science > School of Life Sciences
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ID Code:22200
Deposited On:05 Feb 2016 19:31

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