Octadecaneuropeptide, ODN, protects cerebellar granule neurons against oxidative stress-induced apoptosis
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1
Faculte des Sciences de Tunis, El Manar, Laboratoire de neurophysiologie fonctionnelle et pathologie, 00/UR/08-01, Tunisia
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2
Inserm U413, Universite de Rouen, Laboratoire de Differenciation de Communication Neuronale Neuroendocrine , France
The octadecaneuropeptide (ODN; QATVGDVNTDRPGLLDLK), which has been originally characterized as an endogenous ligand of benzodiazepine receptors, is neurotrophic factor regulating proliferation and/or survival of neuronal cells. Since treatment of neonatal rat by 6-ydroxydopamine (6-OHDA), neurotoxin widely used to produce animal models of Parkinson disease, reduce the immunoreactivity of ODN and delayed migration and degeneration of granule cells in the neocerebellum, we have investigated the ability of ODN to counteract the neurotoxic effects of 6-OHDA on cerebellar granule neurons.
Incubation of granule cells with graded concentrations of 6-OHDA (10 µM - 120 µM) for 72 h provoked a dose-dependent decrease of the proportion of surviving cells. Co-incubation of granule cells with 6-OHDA (30 µM) and graded concentrations of ODN (10-18 M – 10-7 M) for 72 h induced a dose-dependent increase in the number of surviving cells. Complete reversal of the toxic effect of 6-OHDA was observed between 10-16 M and 10-12 M ODN. The neurotoxic effect of 6-OHDA was associated with modifications of granule cell morphology that were suggestive of apoptotic cell death, such as cell shrinkage and nuclear condensation. Treatment of granule cells with 6-OHDA and ODN (10-12M) restored the typical shape of differentiated neurons with bipolar fusiform cell bodies and long neurites. We have also observed that the protective action of ODN (10-12 M) involved the metabotropic receptors types and activated the phosphorylation way of PLC / PKC.
In conclusion, the present study has demonstrated that ODN is a potent protective agent against 6-OHDA-induced oxidative stress and neuronal cell death. The anti-apoptotic effect of ODN can be ascribed to stimulation of SOD activity and thus inhibition of reactive oxygen species accumulation. These data suggest that ODN may have a therapeutic value for the treatment of neuronal death resulting from stress oxidative in neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases.
Supported by research Unit 00/UR/08/01 K.H. was the recipient of a scholarship from the France-Tunisia exchange program Utique-CMCU.
Conference:
3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009.
Presentation Type:
Poster Presentation
Topic:
CNS Diseases
Citation:
Kaddour
H,
Hamdi
Y,
Vaudry
D,
Mokni
M,
Leprince
J,
Vaudry
H,
Tonon
M,
Amri
M and
Masmoudi-Kouki
O
(2009). Octadecaneuropeptide, ODN, protects cerebellar granule neurons against oxidative stress-induced apoptosis.
Front. Neurosci.
Conference Abstract:
3rd Mediterranean Conference of Neuroscience .
doi: 10.3389/conf.neuro.01.2009.16.145
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Received:
25 Nov 2009;
Published Online:
25 Nov 2009.
*
Correspondence:
Hadhemi Kaddour, Faculte des Sciences de Tunis, El Manar, Laboratoire de neurophysiologie fonctionnelle et pathologie, 00/UR/08-01, 2092 Tunis, Tunisia, kaddourhadhemi@yahoo.fr