The octadecaneuropeptide ODN prevents 6-hydroxydopamine-induced apoptosis of cerebellar granule neurons through a PKC-MAPK-dependent pathway - Normandie Université Access content directly
Journal Articles Journal of Neurochemistry Year : 2013

The octadecaneuropeptide ODN prevents 6-hydroxydopamine-induced apoptosis of cerebellar granule neurons through a PKC-MAPK-dependent pathway

Abstract

Oxidative stress, induced by various neurodegenerative diseases, initiates a cascade of events leading to apoptosis, and thus plays a critical role in neuronal injury. In this study, we have investigated the potential neuroprotective effect of the octadecaneuropeptide (ODN) on 6-hydroxydopamine (6-OHDA)-induced oxidative stress and apoptosis in cerebellar granule neurons (CGN). ODN, which is produced by astrocytes, is an endogenous ligand for both central-type benzodiazepine receptors (CBR) and a metabotropic receptor. Incubation of neurons with subnanomolar concentrations of ODN (10⁻¹⁸ to 10⁻¹² M) inhibited 6-OHDA-evoked cell death in a concentration-dependent manner. The effect of ODN on neuronal survival was abrogated by the metabotropic receptor antagonist, cyclo₁₋₈ [DLeu⁵]OP, but not by a CBR antagonist. ODN stimulated polyphosphoinositide turnover and ERK phosphorylation in CGN. The protective effect of ODN against 6-OHDA toxicity involved the phospholipase C/ERK MAPK transduction cascade. 6-OHDA treatment induced an accumulation of reactive oxygen species, an increase of the expression of the pro-apoptotic gene Bax, a drop of the mitochondrial membrane potential and a stimulation of caspase-3 activity. Exposure of 6-OHDA-treated cells to ODN blocked all the deleterious effects of the toxin. Taken together, these data demonstrate for the first time that ODN is a neuroprotective agent that prevents 6-OHDA-induced oxidative stress and apoptotic cell death.

Dates and versions

hal-01962763 , version 1 (20-12-2018)

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Hadhemi Kaddour, Yosra Hamdi, David Vaudry, Magalie Basille, Laurence Desrues, et al.. The octadecaneuropeptide ODN prevents 6-hydroxydopamine-induced apoptosis of cerebellar granule neurons through a PKC-MAPK-dependent pathway. Journal of Neurochemistry, 2013, 125 (4), pp.620-633. ⟨10.1111/jnc.12140⟩. ⟨hal-01962763⟩
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