Impaired Sociability of the Balb/c Mouse, an Animal Model of Autism Spectrum Disorders, is Attenuated by NMDA Receptor Agonist Interventions: Clinical Implications

摘要: Impaired sociability is a domain of psychopathology that contributes significantly to the functional disability and poor quality life persons with Autism Spectrum Disorders (ASDs) (Brodkin, 2007; Crawley, 2004, Deutsch et al., 2011). Although cognitive functioning may influence expression impaired sociability, relationship between deficits not linear one; thus, for example, ASDs whose IQs are in near-normal above normal range manifest profound similar those shown by intellectual (Noterdaeme 2010). Currently, there no approved medications primary target sociability. The N-methyl-D-aspartic acid (NMDA) receptor an example glutamate-gated ion channel comprised four (or possibly five) constituent polypeptide subunits; it located both preand postsynaptically (Millian, 2005). Each integral membrane protein has external, transmembranous internal domains. polypeptides align themselves within lipid bilayer create potential channel, opening depends on binding L-glutamate glycine. duration frequency opening, which results calcium conductance depolarization, highly regulated. properties this ligand-gated influenced genetically combinatorial diversity subunits (i.e., insertion specific their splice variants can affect properties); allosteric modulatory ligands (e.g., neurosteroids) (Deutsch 1992); extent glycosylated nitrosylated; phosphorylated (Marino & Conn, 2002). phosphorylation state cross-talk signaling pathways NMDA receptor; stimulation metabotropic glutamate receptors co-localized cell surface (Conn 2009a; Marino When