y-Aminobutyric acid (GABA) is the neurotransmitter at most inhibitory synapses in the human central nervous system. The GABA, receptor, a ligand-gated ion channel, is the site of action of benzodiazepines, the most widely prescribed neuroactive drugs. It was recently demonstrated that there are multiple subtypes of GABA, receptors. Studies of rodents have shown that receptor subunits are developmentally controlled. The major a subunit of the adult receptor is expressed at low levels before birth. This study, using postmortem human tissue, shows that GABA, receptors are present in significant numbers in the human cerebellum at birth, and the numbers rise threefold by adulthood. TWO subtypes of benzodiazepine receptors were detected by binding studies in the neonate, whereas only a single subtype of receptor was detected in the adult cerebellum. Comparison to recombinant human GABA, receptors shows that receptors containing a1 constitute 50% of the receptors at birth and the percentage rises to over 95% by adulthood.
In both cerebral cortex and cerebellum, a dramatic rise in a1 messenger RNA was observed during development, suggesting that the complement of GABA, receptors differs in infants and adults. These findings have significant implications for normal neurodevelopment as well as for the understanding and treatment of pathophysiological states such as seizures.
Brooks-Kayal AR, Pritchett DB. Developmental changes in human y-aminobutyric aCidA receptor subunit composition.