Title:Neuroprotection with the Endozepine Octadecaneuropeptide, ODN
Volume: 24
Issue: 33
Author(s): Olfa Masmoudi-Kouki*, Yosra Hamdi, Ikram Ghouili, Seyma Bahdoudi, Hadhémi Kaddour, Jérôme Leprince, Hélène Castel, Hubert Vaudry, Mohamed Amri, David Vaudry and Marie-Christine Tonon
Affiliation:
- University Tunis El Manar, Faculty of Science of Tunis, LR18ES03 Laboratory Neurophysiology, Cellular Physiopathology and Biomolecules valorization, 2092 Tunis,Tunisia
Keywords:
Endozepines, ODN, astroglial cells, oxidative injuries, apoptosis, glioprotection, neuroprotection.
Abstract: The term endozepines designates a family of astroglia-secreted proteins including the diazepambinding
inhibitor (DBI) and its processing products, which have been originally isolated and characterized as
endogenous ligands of benzodiazepine receptors. It is now clearly established that the octadecaneuropeptide ODN
(DBI33-50), acting through the central-type benzodiazepine receptor or a metabotropic receptor, exerts important
functions such as proconflict behavior, induction of anxiety, inhibition of pentobarbital-provoked sleep, decrease
of water consumption and reduction of food intake. To mediate its effects, ODN regulates both glial cell and
neuronal activities by acting on neurosteroid biosynthesis and/or neuropeptide expression. In addition, ODN
stimulates astrocyte proliferation and protects both neurons and astrocytes from oxidative stress-induced cell
death. The antiapoptotic effect of ODN on neural cells is mediated through activation of the ODN metabotropic
receptor positively coupled to PKA, PKC and MAPK/ERK transduction pathways, which ultimately reduces the
pro-apoptotic gene Bax and stimulates Bcl-2 expressions, and inhibits intracellular reactive oxygen species accumulation.
The imbalance in favor of Bcl2 promotes mitochondria functions and blocks in turn caspases activation
while at the same time, ODN also activates the endogenous antioxidant system i.e. glutathione biosynthesis, and
expression and activities of antioxidant enzymes. In cultured astrocytes, DBI expression is up-regulated during
moderate oxidative stress, and authentic ODN production is increased, suggesting that ODN may act as a
paracrine factor protecting neighboring neurons. Taken together, the remarkable effect of ODN on the apoptotic
cascade suggests that innovative ODN derivatives could potentially be useful for treatment of cerebral injuries
involving oxidative stress and neurodegeneration.
