Changes in glial glutamate transporters in human epileptogenic hippocampus: inadequate explanation for high extracellular glutamate during seizures.
Temporal lobe epilepsy (TLE) with hippocampal sclerosis is associated with high extracellular glutamate levels, which could trigger seizures. Down-regulation of glial glutamate transporters GLAST (EAAT1) and GLT-1 (EAAT2) in sclerotic hippocampi may account for such increases. Their distribution was compared immunohistochemically in non-sclerotic and sclerotic hippocampi and localized only in astrocytes, with weaker immunoreactivity for both transporters in areas associated with pronounced neuronal loss, especially in CA1, but no decrease or even an increase in areas with less neuronal loss, like CA2 and the subiculum in the sclerotic group. Such compensatory changes in immunoreactivity may account for the lack of differences between the groups in immunoblot studies as blots show the average concentrations in the samples. These data suggest that differences in glial glutamate transporter distribution between the two groups of hippocampi may be an insufficient explanation for the high levels of extracellular glutamate in sclerotic seizure foci observed through in vivo dialysis studies.
Bjørnsen
L P
LP
CMBN at Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Blindern, Norway.
Eid
T
T
Holmseth
S
S
Danbolt
N C
NC
Spencer
D D
DD
de Lanerolle
N C
NC
D000293:Adolescent; D000328:Adult; D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism* / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation / Q000502:physiology; D004827:Epilepsy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D015854:Up-Regulation / Q000502:physiology
D027322:Amino Acid Transport System X-AG; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D018698:Glutamic Acid