Age-related changes in brainstem auditory neurotransmitters: Measures of GABA and acetylcholine function

Ahmad Raza, Joseph C. Milbrandt, Stephen P. Arneric, Donald M. Caspary

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

This study was designed to determine if there are age-related alterations 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 neuronal 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 activity 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). Choline acetyltransferase (ChAT) activity was highest in NLL and CN, and approximately 35-40% lower in CIC. A more uniform pattern was observed with GABA-T activity. Reductions in GAD activity were seen in the CIC of mature (-31%) and aged (-30%) rats that were not graded with 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 ChAT activity. The neurotransmitter selectivity of this deficit in CIC is supported by the non-parallel changes in ChAT activity (-22%, aged vs. 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 (Kd and Vmax) for 14C-GABA and 3H-d-aspartate were not significantly altered (P > 0.05). Similar to the CIC, 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 activity with aging. These data suggest: 1) Age-related loss of GABA-mediated inhibition in the CIC of Fischer-344 rats is not attributable to changes in uptake or degradation of GABA, but may be related loss of biosynthetic capacity (i.e. activity or quantity) of the GAD present; 2) processing centers of the central auditory pathway (i.e. CIC and NLL), but not necessarily primary (i.e. CN) integrativc nuclei, demonstrate selective, age-related neurochemical deficits; and 3) age-related neurochemical changes in central auditory structures may contribute substantially to the abnormal perception of signals in noise and loss of speech discrimination observed in neural presbycusis.

Original languageEnglish (US)
Pages (from-to)221-230
Number of pages10
JournalHearing Research
Volume77
Issue number1-2
DOIs
StatePublished - Jun 15 1994

Fingerprint

Glutamate Decarboxylase
Cochlear Nucleus
gamma-Aminobutyric Acid
Brain Stem
Acetylcholine
Neurotransmitter Agents
4-Aminobutyrate Transaminase
Young Adult
Choline O-Acetyltransferase
Inbred F344 Rats
Cholinergic Agents
Presbycusis
Auditory Pathways
Inferior Colliculi
Speech Perception
Proteins
Enzymes
Noise
Pontine Tegmentum

Keywords

  • Aging
  • Central auditory
  • Cochlear nucleus
  • GABA
  • GAD
  • Inferior colliculus

ASJC Scopus subject areas

  • Sensory Systems

Cite this

Age-related changes in brainstem auditory neurotransmitters : Measures of GABA and acetylcholine function. / Raza, Ahmad; Milbrandt, Joseph C.; Arneric, Stephen P.; Caspary, Donald M.

In: Hearing Research, Vol. 77, No. 1-2, 15.06.1994, p. 221-230.

Research output: Contribution to journalArticle

Raza, Ahmad ; Milbrandt, Joseph C. ; Arneric, Stephen P. ; Caspary, Donald M. / Age-related changes in brainstem auditory neurotransmitters : Measures of GABA and acetylcholine function. In: Hearing Research. 1994 ; Vol. 77, No. 1-2. pp. 221-230.
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N2 - This study was designed to determine if there are age-related alterations 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 neuronal 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 activity 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). Choline acetyltransferase (ChAT) activity was highest in NLL and CN, and approximately 35-40% lower in CIC. A more uniform pattern was observed with GABA-T activity. Reductions in GAD activity were seen in the CIC of mature (-31%) and aged (-30%) rats that were not graded with 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 ChAT activity. The neurotransmitter selectivity of this deficit in CIC is supported by the non-parallel changes in ChAT activity (-22%, aged vs. 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 (Kd and Vmax) for 14C-GABA and 3H-d-aspartate were not significantly altered (P > 0.05). Similar to the CIC, 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 activity with aging. These data suggest: 1) Age-related loss of GABA-mediated inhibition in the CIC of Fischer-344 rats is not attributable to changes in uptake or degradation of GABA, but may be related loss of biosynthetic capacity (i.e. activity or quantity) of the GAD present; 2) processing centers of the central auditory pathway (i.e. CIC and NLL), but not necessarily primary (i.e. CN) integrativc nuclei, demonstrate selective, age-related neurochemical deficits; and 3) age-related neurochemical changes in central auditory structures may contribute substantially to the abnormal perception of signals in noise and loss of speech discrimination observed in neural presbycusis.

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