Age-related changes in GABA(A) receptor subunit composition and function in rat auditory system

A decline in the ability to discriminate speech from noise due to age-relat ed hearing loss (presbycusis) may reflect impaired auditory information pro cessing within the central nervous system. Presbycusis may result, in part, from functional loss of the inhibitory neurotransmitter GABA. The present study assessed age-related changes of the GABA(A) receptor in the inferior colliculus of young-adult, middle-aged, and aged rats related to: (i) recep tor subunit composition and (ii) receptor function. Western blotting was us ed to measure protein levels of selected GABA(A), receptor subunits in prep arations obtained from the inferior colliculus of Fischer 344 and Fischer 3 44/Brown-Norway F1 hybrid rats. In both strains, the aged group exhibited s ignificant increases in gamma(1) subunit protein and a decrease in alpha(1) subunit protein. To examine the functional consequence of this putative ag e-related subunit change, we measured the ability of exogenous GABA to flux /translocate chloride ions into microsac preparations derived from Fischer 344 inferior colliculus. GABA-mediated chloride influx was significantly in creased in samples prepared from the inferior colliculus of aged animals. Together with previous studies, these results strongly suggest an age-relat ed change in GABA(A) receptor composition. These changes may reflect a comp ensatory up-regulation of inhibitory function in the face of significant lo ss of presynaptic GABA release. These findings provide one example of plast ic neurotransmitter receptor changes which can occur during the ageing proc ess. (C) 1999 IBRO. Published by Elsevier Science Ltd.