[Role of glutamate transporters in the pathophysiology of major mental illnesses].

Abnormalities in L-glutamate signal transmission have been postulated to play a role in major mental illnesses. The glial disruption results in decreased uptake of glutamate and an elevation of extracellular glutamate levels. Elevated extracellular glutamate may cause cytotoxic damage to neurons and glia. Significant down-regulation of glial glutamate transporters, GLT1 and GLAST, in major depressive disorder has been reported. In the present study we examined the role of glial glutamate transporters in the pathogenesis of autism and schizophrenia. We generated animal models in which glutamate receptors are overstimulated by genetic down-regulation of glial glutamate transporters. Resulting mutant mice showed abnormal social interaction, increased anxiety-like behavior, and select phenotypic abnormalities related to the negative and cognitive symptoms of schizophrenia. We observed enlarged amygdala and hippocampus. These mutant mice replicate many aspects of the behavioral and neuroanatomical abnormalities seen in autism and schizophrenia. Thus, these mutants are new animal models of major mental illness.