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 transporters have been identified in human brain: EAAT1, EAAT2, EAAT3, and EAAT4. Deficient glutamate transport has been identified in the motor cortex and the spinal cord of tissue from amyotrophic lateral sclerosis (ALS) patients. The defect appears to be due to a selective loss of the astroglial specific glutamate transporter protein EAAT2. In these studies we sought to extend our understanding of glutamate transporters in ALS by examining the mRNA for each transporter subtype in ALS motor cortex. All tissue was matched for age and postmortem delay. There was no quantitative change in mRNA for EAAT1, EAAT2, or EAAT3 in ALS motor cortex, even in patients with a large loss of EAAT2 protein (95% decrease compared with control) and decreased tissue glutamate transport (73% decrease compared with control). These studies suggest that the dramatic abnormalities in EAAT2 may be due to translational or post-translational processes.
Bristol
L A
LA
Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Rothstein
J D
JD
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000367:Age Factors; D000368:Aged; D027322:Amino Acid Transport System X-AG; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism; D001344:Autopsy; D001692:Biological Transport / Q000235:genetics; D015152:Blotting, Northern; D027342:Excitatory Amino Acid Transporter 2; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000737:chemistry* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D017981:Receptors, Neurotransmitter / Q000235:genetics*
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D027342:Excitatory Amino Acid Transporter 2; D012333:RNA, Messenger; D017981:Receptors, Neurotransmitter