GABA(A)-receptor mRNA expression in the prefrontal and temporal cortex of ALS patients

J Neurol Sci. 2006 Dec 1;250(1-2):124-32. doi: 10.1016/j.jns.2006.08.005. Epub 2006 Oct 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Biomarkers / metabolism
  • Down-Regulation / genetics
  • Gene Expression / physiology
  • Glutamate Decarboxylase / genetics
  • Humans
  • Middle Aged
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Neural Inhibition / genetics
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / physiopathology
  • RNA, Messenger / metabolism*
  • Receptors, GABA-A / genetics*
  • Temporal Lobe / metabolism*
  • Temporal Lobe / physiopathology
  • Up-Regulation / genetics
  • gamma-Aminobutyric Acid / biosynthesis


  • Biomarkers
  • GABRA1 protein, human
  • RNA, Messenger
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid
  • Glutamate Decarboxylase