Cell Death Mediated by Amino Acid Transmitter Receptors in Human Alcoholic Brain Damage: Conflicts in the Evidencea

Abstract

Human alcoholics have reduced neuronal counts in certain brain regions, such as superior frontal cortex (SFC), where the form and quantity of synaptic γ-aminobutyric acid type A (GABA_A) receptor sites are atypical. We measured the expression of GABA_A receptor isoform mRNA and protein, since GABA_A receptor pharmacology is strongly influenced by its subunit composition. Cortex samples were obtained at autopsy; whole-tissue extracts were assayed for mRNA by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), while synaptic membranes were studied for both GABA_A receptor pharmacology and subunit protein levels by Western blots with isoform-specific antibodies. Although α₁ and α₃ mRNA species were more strongly expressed in alcoholics irrespective of cirrhosis than in controls, α₁ protein differed little between case groups, and α₃ protein showed some complex variations. Differences in GABA_A pharmacology conformed more closely with differences in protein levels than with altered mRNA expression.