Octadecaneuropeptide promotes the migration of astrocyte via ODN metabotropic receptor and calcium signaling pathway.

Abstract

Migration is an essential characteristic of cells that occurs during many physiological and pathological processes. Astrocytes represent the most abundant cell type in the adult central nervous system (CNS), that play a crucial role in various functions such as guiding and supporting neuronal migration during development and maintaining brain homeostasis at adulthood. Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides, including the octadecaneuropeptide (ODN). ODN is an endogenous ligand for both central-type benzodiazepine receptors and a metabotropic receptor. ODN promotes proliferation and prevents oxidative damage induced apoptosis on both neurons and astrocytes. However, little is known regarding the effect of ODN on cell migration. The purpose of the present study was to investigate the potential effect of ODN on astrocytes migration. Our results show that ODN stimulates astrocytes proliferation and migration at very low concentrations in wound healing assays, that was mimicked by the metabotropic ODN receptor agonist cyclo_1-8 octapeptide (cyclo_1-8OP, 10^-14 M to 10^-10 M). The effect of ODN on astrocyte migration was abrogated by the metabotropic receptor antagonist, cyclo_1-8[DLeu⁵] OP. Moreover, we have shown that ODN activates the calcium signaling pathway and increases the mammalian target of rapamycin (mTOR) gene transcription, which are both known to promote astrocyte migration. Therefore, the present results suggest that ODN regulates astroglial cell migration through the calcium/mTOR signaling pathway and provide new insight regarding the role of ODN on brain remodling after injury.