Alterations of GABAA receptor subunit mRNA levels in the aging Fischer 344 rat inferior colliculus.
The inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) is critically involved in shaping neuronal responses to simple and complex acoustic stimuli in the central auditory structure, the inferior colliculus (IC). Studies in rat and human suggest that age-related changes in markers for GABA neurotransmission occur in the IC. In particular, these changes include findings indicative of an age-related increase in the efficacy/potency of GABA to inhibit ligand binding at the GABAA receptor picrotoxin site in the Fischer (F344) rat IC. Such changes in GABAA receptor modulation suggest the potential for an alteration in GABAA receptor subunit composition in the old rat IC. To test this idea, the present study used in situ hybridization to quantify age-related changes in GABAA receptor subunit mRNA levels in the three major subdivisions of the IC in the F344 rat: dorsal cortex (DCIC), external cortex (ECIC), and the central nucleus (CIC). In support of earlier findings of an age-related change in GABAA receptor modulation, the present study found: (1) GABAA receptor subunit mRNA levels were significantly altered in the IC of old rats, and (2) age-related changes in subunit levels appeared to be regionally selective and subunit specific. A highly significant increase in the level of the gamma 1 subunit mRNA was observed with little change in the levels of the alpha 1, beta 2, and gamma 2 subunit mRNAs. A nonstatistically significant increase in alpha 2 subunit mRNA was also observed. This observed increase in alpha 2 subunit mRNA could be important since previous expression studies have shown that the alpha 2 and gamma 1 subunits coassemble and are incorporated into GABAA receptors which appear to be more sensitive to GABA. If the observed changes in subunit mRNA levels with age correlate well with enhanced GABAA receptor function in the IC of old rats, this, in turn, may represent a compensatory mechanism in response to presynaptic GABAergic changes.
Milbrandt
J C
JC
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield 62702, USA.
Hunter
C
C
Caspary
D M
DM
D000375:Aging / Q000378:metabolism*; D000818:Animals; D017403:In Situ Hybridization; D007245:Inferior Colliculi / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011963:Receptors, GABA-A / Q000378:metabolism*
D012333:RNA, Messenger; D011963:Receptors, GABA-A