Intrahippocampal administration of an antibody against glycoprotein M6a impairs memory consolidation in an inhibitory avoidance task in mice

MARÍA DEL CARMEN KRAWCZYK; MICAELA D GARCÍA; MILLÁN JULIETA; ALBERTO C FRASCH; MARIANO M BOCCIA; CAMILA SCORTICATI

Ciudad Autónoma de Buenos Aires

Congreso; FALAN 2016; 2016

FALAN 2016

Membrane glycoprotein M6a, together with M6b, proteolipid protein (PLP) and DM20, belongs to the PLP family and has been related to neuronal plasticity in different experimental models. In mice and treeshrews, Gpm6a has been identified as a chronic stress-regulated gene. Besides, knockout mice for Gpm6a/Gpm6b show decreased axon elongation and a thinner corpus callosum concomitantly with a claustrophobia phenotype. M6a is composed by 278 aminoacids that form four transmembrane domains, two external loops (EC1 and EC2), and the N- and C-terminal regions facing the cell cytoplasm. M6a positive contributes to neurite, axon, filopodium/spine and synapse formation in both primary cultured of hippocampal neurons and cell lines. Many studies have been conducted to determine the importance of M6a structure in its function. Regarding to EC2, in vitro studies showed that specific features of the major external loop and their epitope recognition modified M6a function. To date, no natural ligands of M6a or binding partners have been found, so monoclonal antibodies against EC2 (M6a-mAB) have been used to block M6a function. To assess its potential role in memory processes, we injected M6a-mAb (3.0 ? 30.0 ng/hip) or IgG isotype into the hippocampus of CF-1 male mice immediately or 180 m after training in an inhibitory avoidance task. Memory retention was tested 48 h afterwards. M6a-mAb (30.0 ng/hip) impaired performance on the testing day in a dose- and time-dependent manner. Altogether, these results suggest that M6a-mAb might impairs memory consolidation of an inhibitory avoidance task in mice, letting us to speculate a critical role of M6a on synaptic plasticity induced by learning and memory processes.