Alternative splicing of glutamate transporter EAAT2 RNA in neocortex and hippocampus of temporal lobe epilepsy patients.
BACKGROUND
Altered expression of glutamate transporter EAAT2 protein has been reported in the hippocampus of patients with temporal lobe epilepsy (TLE). Two alternative EAAT2 mRNA splice forms, one resulting from a partial retention of intron 7 (I7R), the other from a deletion of exon 9 (E9S), were previously implicated in the loss of EAAT2 protein in patients with amyotrophic lateral sclerosis.


METHODS
By RT-PCR we studied the occurrence of I7R and E9S in neocortical and hippocampal specimens from TLE patients and non-neurological controls.


RESULTS
Both splice forms were found in all neocortical specimens from TLE patients (100% I7R, 100% E9S). This was significantly more than in controls (67% I7R, 60% E9S; P < 0.05). We also detected I7R and E9S in all seven motor cortex post-mortem samples from patients with amyotrophic lateral sclerosis. Within the TLE patient group, both splice variants appeared significantly more in non-sclerotic (100%), than in sclerotic hippocampi (69%, P < 0.05).


CONCLUSIONS
These data indicate that the epileptic brain, especially that of TLE patients without hippocampal sclerosis, is highly prone to alternative EAAT2 mRNA splicing. Our data confirm that the presence of alternative EAAT2 splice forms is not disease specific.
Hoogland
G
G
Rudolf Magnus Institute for Neurosciences, University Medical Center Utrecht, P.O. Box 85500, Utrecht AB 3508, The Netherlands.
van Oort
R J
RJ
Proper
E A
EA
Jansen
G H
GH
van Rijen
P C
PC
van Veelen
C W M
CW
van Nieuwenhuizen
O
O
Troost
D
D
de Graan
P N E
PN
D000328:Adult; D000368:Aged; D017398:Alternative Splicing / Q000235:genetics* / Q000502:physiology; D016009:Chi-Square Distribution; D004833:Epilepsy, Temporal Lobe / Q000235:genetics* / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics* / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
D027342:Excitatory Amino Acid Transporter 2; D020033:Protein Isoforms; D012333:RNA, Messenger