Human spinal motoneurons express low relative abundance of GluR2 mRNA: an implication for excitotoxicity in ALS

• Published in: Journal of neurochemistry Vol. 85; no. 3; pp. 680 - 689
• Main Authors: Kawahara, Yukio, Kwak, Shin, Sun, Hui, Ito, Kyoko, Hashida, Hideji, Aizawa, Hitoshi, Jeong, Seon‐Yong, Kanazawa, Ichiro
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.05.2003; Blackwell
• Subjects: Adult; Aged; ALS; AMPA receptor; Amyotrophic Lateral Sclerosis - etiology; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - pathology; Biological and medical sciences; Cell Separation - instrumentation; Cell Separation - methods; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; excitotoxicity; Female; GluR2; Glutamic Acid - metabolism; Humans; Lasers; Male; Medical sciences; Middle Aged; Motor Neurons - metabolism; Motor Neurons - pathology; Neurology; Neurotoxins - metabolism; Protein Subunits - genetics; Purkinje Cells - metabolism; Purkinje Cells - pathology; Pyramidal Cells - metabolism; Pyramidal Cells - pathology; quantitative RT–PCR; Receptors, AMPA - genetics; Receptors, Glutamate - genetics; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; RNA Editing; RNA, Messenger - biosynthesis; Spinal Cord - metabolism; Spinal Cord - pathology; Human; Nervous system diseases; Spinal cord; RNA editing; ALS; Amyotrophic lateral sclerosis; Glutamate receptor; Motor neuron; GluR2; Gene expression; Subunit; Genetic disease; Toxin; AMPA receptor; Animal; Central nervous system disease; Neurotoxin; quantitative RT-PCR; Degenerative disease; excitotoxicity; Spinal cord disease
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2003.01703.x

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.