GLUTAMATE TRANSPORTER GENE-EXPRESSION IN AMYOTROPHIC-LATERAL-SCLEROSIS MOTOR CORTEX

Glutamate transport is critical for synaptic inactivation of glutamate and prevention of excitotoxicity. The following four glutamate transp orters have been identified in human brain: EAAT1, EAAT2, EAAT3, and E AAT4. Deficient glutamate transport has been identified in the motor c ortex and the spinal cord of tissue from amyotrophic lateral sclerosis (ALS) patients. The defect appears to be due to a selective loss of t he astroglial specific glutamate transporter protein EAAT2. In these s tudies we sought to extend our understanding of glutamate transporters in ALS by examining the mRNA for each transporter subtype in ALS moto r cortex. All tissue was matched for age and postmortem delay. There w as no quantitative change in mRNA for EAAT1, EAAT2, or EATT3 in ALS mo tor cortex, even in patients with a large loss of EAAT2 protein (95% d ecrease compared with control) and decreased tissue glutamate transpor t (73% decrease compared with control). These studies suggest that the dramatic abnormalities in EAAT2 may be due to translational or posttr anslational processes.