GABA(A)-receptor mRNA expression in the prefrontal and temporal cortex of ALS patients.
There is evidence that excitotoxic cell death is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Electrophysiological and histological studies support the pathophysiological concept of an impaired inhibitory, namely GABAergic, control of the motoneurons in the cerebral cortex of ALS patients. Recently, pathological, neuropsychological and functional imaging data have challenged the view that ALS is a disorder restricted to the motor system. The aim of our study was to investigate the expression of the most abundant GABA(A)-receptor subunit mRNAs and the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) in the prefrontal, temporal, occipital and cerebellar cortex of ALS patients compared to tissue of control persons. We performed in situ hybridization histochemistry (ISH) on human post-mortem cortex sections of ALS patients (n=5) and age-matched controls with no history of neurological disease (n=5). In the prefrontal and temporal cortex of ALS patients, we detected significantly reduced mRNA expression of the alpha1-subunit, while the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) was significantly upregulated in these regions. In the occipital and cerebellar cortex, we did not see disease-specific differences of the mRNA expression of the investigated subunits.
Petri
Susanne
S
Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30623 Hannover, Germany. petri.susanne@MH-Hannover.de
Kollewe
Katja
K
Grothe
Claudia
C
Hori
Akira
A
Dengler
Reinhard
R
Bufler
Johannes
J
Krampfl
Klaus
K
D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009433:Neural Inhibition / Q000235:genetics; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000235:genetics*; D013702:Temporal Lobe / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
D015415:Biomarkers; C546240:GABRA1 protein, human; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase