Glutamate transporter EAAT2 splice variants occur not only in ALS, but also in AD and controls.
OBJECTIVE
To ascertain the specificity of alternatively spliced mRNA variants of the astroglial glutamate transporter EAAT2 for ALS.


BACKGROUND
An important hypothesis for ALS pathogenesis is that motor neuron injury may result from chronically elevated glutamate levels in the CNS. Supporting this idea are reports of decreased glutamate transport in ALS. This in turn has recently been suggested to be due to the presence of aberrant mRNA splice variants for EAAT2 in ALS.


METHODS
Postmortem human brain tissue was obtained from different brain regions of patients with ALS, normal controls (NC), and patients with AD and Lewy body dementia (LB)-neurodegenerative diseases in which motor neurons are unaffected. Brain RNA was analyzed for EAAT2 isoforms using reverse transcription PCR and cDNA cloning/sequencing methods.


RESULTS
Splice variants lacking exons 7 or 9 were present in ALS brain, as previously reported, but were also present in brains from NC, AD, and LB patients. PCR product sequence analyses from non-ALS brain show variant splicing identical to that reported for ALS. Quantitative PCR analysis shows that these isoforms may be somewhat more abundant in ALS than AD, LB, and NC brains.


CONCLUSIONS
EAAT2 mRNA splice variants are found in the brains of NC and AD patients, as in ALS. The authors cannot exclude the possibility that quantitative changes in variant EAAT2 isoforms might relate directly, or indirectly, to ALS pathology. However, the qualitative presence of these "abnormal" EAAT2 splice variants does not appear to be sufficient to explain motor neuron degeneration in ALS.
Honig
L S
LS
Department of Neurology, University of Texas Southwestern Medical Center at Dallas, USA. lhonig@sergievsky.cpmc.columbia.edu
Chambliss
D D
DD
Bigio
E H
EH
Carroll
S L
SL
Elliott
J L
JL
D017398:Alternative Splicing / Q000235:genetics*; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D001923:Brain Chemistry / Q000235:genetics; D027342:Excitatory Amino Acid Transporter 2; D006801:Humans; D016133:Polymerase Chain Reaction; D017981:Receptors, Neurotransmitter / Q000235:genetics*
D027342:Excitatory Amino Acid Transporter 2; D017981:Receptors, Neurotransmitter