AGE-RELATED-CHANGES IN BRAIN-STEM AUDITORY NEUROTRANSMITTERS - MEASURES OF GABA AND ACETYLCHOLINE FUNCTION

This study was designed to determine if there are age-related alterati ons in the bio-synthetic enzyme glutamic acid decarboxylase (GAD), the degradative enzyme GABA-transaminase (GABA-T), and the uptake system for GABA in the central nucleus of the inferior colliculus (CIC), the cochlear nucleus (CN), and/or nuclei of the lateral lemniscus (NLL) of Fischer-344 rats. For purposes of comparison, the cholinergic neurona l system was studied in parallel in young adult (3-7 months), mature ( 15-17 months) and aged (24-26 months) rats. In young adults GAD activi ty was highest in the CIC (219 nmol/mg protein/h; N = 5), intermediate in NLL (82 nmol/mg protein/h), and lowest in CN (34 nmol/mg protein/h ). Chorine acetyltransferase (ChAT) activity was highest in NLL and CN , and approximately 35-40% lower in CIC. A more uniform pattern was ob served with GABA-T activity. Reductions in GAD activity were seen in t he CIC of mature (- 31%) and aged (- 30%) rats that were not graded wi th age when compared to young adult, P < 0.05 (N= 5). This effect was regionally selective, since the CN did not show any loss of GAD or ChA T activity. The neurotransmitter selectivity of this deficit in CIC is supported by the non-parallel changes in ChAT activity (- 22%, aged v s. mature, P < 0.05) that occurred after the changes in GAD activity. In contrast to the loss of GABAergic biosynthetic capacity in aged CIC , high affinity uptake processes (K-d and V-max) for C-14-GABA and H-3 -d-aspartate were not significantly altered (P<0.05). Similar to the C IC, the NLL showed remarkable age-related deficits, but these deficits were more substantial for the cholinergic system (ChAT activity: -56% aged vs. young adult, P < 0.05; GAD activity: -35% aged vs. mature). None of the areas examined showed a significant loss of GABA-T activit y with aging. These data suggest: 1) Age-related loss of GABA-mediated inhibition in the CIC of Fischer-344 rats is not;attributable to chan ges in uptake or degradation of GABA, but may be related loss of biosy nthetic capacity (i.e. activity or quantity) of the GAD present; 2) pr ocessing centers of the central auditory pathway (i.e. CIC and NLL), b ut not necessarily primary (i.e. CN) integrative nuclei, demonstrate s elective, age-related neurochemical deficits; and 3) age-related neuro chemical changes in central auditory structures may contribute substan tially to the abnormal perception of signals in noise and loss of spee ch discrimination observed in neural presbycusis.