title: Age-related changes in GABA(A) receptor subunit composition and function in rat auditory system.
abstract: A decline in the ability to discriminate speech from noise due to age-related hearing loss (presbycusis) may reflect impaired auditory information processing 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) receptor subunit composition and (ii) receptor function. Western blotting was used to measure protein levels of selected GABA(A) receptor subunits in preparations obtained from the inferior colliculus of Fischer 344 and Fischer 344/Brown-Norway F1 hybrid rats. In both strains, the aged group exhibited significant increases in gamma1 subunit protein and a decrease in alpha1 subunit protein. To examine the functional consequence of this putative age-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 increased in samples prepared from the inferior colliculus of aged animals. Together with previous studies, these results strongly suggest an age-related change in GABA(A) receptor composition. These changes may reflect a compensatory up-regulation of inhibitory function in the face of significant loss of presynaptic GABA release. These findings provide one example of plastic neurotransmitter receptor changes which can occur during the ageing process.
authors.affiliation: Southern Illinois University School of Medicine, Springfield 62794-9629, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Caspary
authors.forename: T M
authors.initials: TM
authors.lastname: Holder
authors.forename: L F
authors.initials: LF
authors.lastname: Hughes
authors.forename: J C
authors.initials: JC
authors.lastname: Milbrandt
authors.forename: R M
authors.initials: RM
authors.lastname: McKernan
authors.forename: D K
authors.initials: DK
authors.lastname: Naritoku
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002712:Chlorides / Q000378:metabolism; D006309:Hearing / Q000502:physiology*; D017403:In Situ Hybridization; D007245:Inferior Colliculi / Q000254:growth & development / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D002712:Chlorides; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid