Distribution of GABAA receptor mRNA in the motor cortex of ALS patients.
The pathomechanism of amyotrophic lateral sclerosis (ALS) remains unclear. There is some evidence that excitotoxic cell death is involved in the degeneration of the motor nervous system, and that ligand-gated receptor channels play a role in the pathogenesis of the disease. Several electrophysiological and anatomical studies support the pathophysiological concept of an impaired inhibitory, namely GABAergic, control of the motoneurons in the cerebral cortex of ALS patients. The aim of our study was to investigate the expression of GABAA-receptor subunit mRNAs and the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) in the motor cortex of ALS patients compared to tissue of control persons. We performed in situ hybridization histochemistry (ISH) on human postmortem motor cortex sections of ALS patients (n = 5) and age matched controls with no history of neurological disease (n = 5). The most intriguing finding was a significantly reduced mRNA expression of the alpha1-subunit in ALS patients while the level of beta1-subunit mRNA was elevated in the patients group. This may indicate specific alterations of the GABAA receptor subunit composition and result in distinct physiological and pharmacological properties of these receptors in ALS patients.
Petri
Susanne
S
Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30623 Hannover, Germany. petri.susanne@MH-Hannover.de
Krampfl
Klaus
K
Hashemi
Fariba
F
Grothe
Claudia
C
Hori
Akira
A
Dengler
Reinhard
R
Bufler
Johannes
J
D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D001345:Autoradiography; D016022:Case-Control Studies; D002452:Cell Count; D048429:Cell Size; D005820:Genetic Testing; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009044:Motor Cortex / Q000166:cytology / Q000378:metabolism*; D010147:Pain Measurement; D021122:Protein Subunits / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D011963:Receptors, GABA-A / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D021122:Protein Subunits; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D005968:Glutamate Decarboxylase