Human spinal motoneurons express low relative abundance of GluR2 mRNA: an implication for excitotoxicity in ALS.
AMPA receptor-mediated neurotoxicity is currently the most plausible hypothesis for the etiology of amyotrophic lateral sclerosis (ALS). The mechanism initiating this type of neuronal death is believed to be exaggerated Ca2+-influx through AMPA receptors, which is critically determined by the presence or absence of the glutamate receptor subunit 2 (GluR2) in the assembly. We have provided the first quantitative measurements of the expression profile of AMPA receptor subunits mRNAs in human single neurons by means of quantitative RT-PCR with a laser microdissector. Among the AMPA subunits, GluR2 shared the vast majority throughout the neuronal subsets and tissues examined. Furthermore, both the expression level and the proportion of GluR2 mRNA in motoneurons were the lowest among all neuronal subsets examined, whereas those in motoneurons of ALS did not differ from the control group, implying that selective reduction of the GluR2 subunit cannot be a mechanism of AMPA receptor-mediated neurotoxicity in ALS. However, the low relative abundance of GluR2 might provide spinal motoneurons with conditions that are easily affected by changes of AMPA receptor properties including deficient GluR2 mRNA editing in ALS.
Kawahara
Yukio
Y
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo, Japan.
Kwak
Shin
S
Sun
Hui
H
Ito
Kyoko
K
Hashida
Hideji
H
Aizawa
Hitoshi
H
Jeong
Seon-Yong
SY
Kanazawa
Ichiro
I
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002469:Cell Separation / Q000295:instrumentation / Q000379:methods; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007834:Lasers; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology; D017393:RNA Editing; D012333:RNA, Messenger / Q000096:biosynthesis*; D018091:Receptors, AMPA / Q000235:genetics*; D017470:Receptors, Glutamate / Q000235:genetics; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology
D009498:Neurotoxins; D021122:Protein Subunits; D012333:RNA, Messenger; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018698:Glutamic Acid; C104722:glutamate receptor ionotropic, AMPA 2