Functional role of a specific ganglioside in neuronal migration and neurite outgrowth

Abstract

Cell migration occurs extensively during mammalian brain development and persists in a few regions in the adult brain. Defective migratory behavior of neurons is thought to be the underlying cause of several congenital disorders. Knowledge of the dynamics and molecular mechanisms of neuronal movement could expand our understanding of the normal development of the nervous system as well as help decipher the pathogenesis of neurological developmental disorders. In our studies we have identified and characterized a specific ganglioside (9-O-acetyl GD3) localized to the membrane of neurons and glial cells that is expressed in regions of cell migration and neurite outgrowth in the developing and adult rat nervous system. In the present article we review our findings that demonstrate the functional role of this molecule in neuronal motility.

Structural analysis of brain ganglioside acetylation patterns in mice with altered ganglioside biosynthesis

“…The acetylation of GD3, the fraction heavily accumulated in GM2/GD2 synthase-deficient mice, was previously confirmed by immunohistochemical localization and mass spectrometry in studies by Matsuda et al 23 and Furukawa et al 24 We did not detect O-Ac-GD3 in wt mouse brain tissue since it is a very minor ganglioside in the adult brain, while in developing brain, the expression of O-Ac-GD3 has been associated to processes such as neurite outgrowth and neuronal migration in mammalian brain. [31][32][33] Interestingly, it was found that exogenously added GD3 induces its own O-acetylation machinery in different cell types, 34 while other gangliosides fail to induce the same machinery. This finding implies that O-acetylation machinery requires very specific oligosaccharide moieties of gangliosides and that not all ganglioside species are susceptible to O-acetylation in the same proportion.…”

GM1 induces p38 and microtubule dependent ramification of rat primary microglia in vitro

“…1B) and LPS-and IFN-γ-treated microglia (data not shown). Furthermore, several studies indicated that gangliosides increase the rates of neuritogenesis both in vivo and in vitro (Ferrari et al, 1983;Mendez-Otero and Santiago, 2003;Roisen et al, 1984) and possess a neuroprotective action (Favaron et al, 1988;Geisler et al, 1991;Karpiak et al, 1990;Manev et al, 1990;Seren et al, 1990). These effects have partly been explained by the fact that GM1 induces a rapid and significant increase in the amount of NT-3, which was observed in fibroblast cells and cerebellar granule cells (Rabin et al, 2002).…”

Sphingolipids: membrane microdomains in brain development, function and neurological diseases

“…Early in the developing rat nervous system the expression of a variant of GD3, 9-O-acetyl GD3, appears to be involved in glial-guided neuronal migration and neurite outgrowth [80]. A similar role might be performed by GM1 in the early stages of the human brain development as GM1 has been implicated in glial-neuronal contacts during the migration of neuroblasts [81].…”