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Cited by 235Hearing, Cochlea, Tinnitus, GeneticsNeuroscience and Neuropharmacology ResearchVestibular and auditory disorders

Immunocytochemical and neurochemical evidence for age-related loss of GABA in the inferior colliculus: implications for neural presbycusis.

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Caspary, DM, Raza, A, Lawhorn Armour, BA, Pippin, J, Arneric, SP·1990·The Journal of Neuroscience
DOI 10.1523/jneurosci.10-07-02363.1990PMC PMC6570369
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Abstract

The present study describes substantial, selective, age-related loss of the putative inhibitory neurotransmitter GABA in the central nucleus of the inferior colliculus (CIC) of rat based on immunocytochemical and neurochemical data. For immunocytochemistry, neurons in the CIC were immunolabeled using an antibody against a GABA conjugate in young adult (2- to 7-month-old) and aged (18- to 29-month-old) Fischer-344 rats. Computer-assisted morphometry was then used to generate maps of GABA- immunoreactive neurons in the CIC. The number of GABA-positive neurons was reduced 36% in the ventrolateral portion of the CIC of aged animals (93 neurons/mm2) compared to their matched young adult cohorts (145 neurons/mm2; p less than 0.01). For neurochemistry, basal and K(+)- evoked release of the endogenous amino acids GABA, glutamate (Glu), aspartate (Asp), and tyrosine (Tyr) from micropunches of the CIC were measured in 8 age-paired animals from the 2 age groups using high- performance liquid chromatography. Overflow of radiolabeled acetylcholine (3H-ACh) was also determined. In both age groups, K(+)- evoked release of GABA, Glu, Asp, and 3H-ACh from CIC punches was significantly enhanced above basal efflux (+200, +215, +163, and +309%, respectively), while Tyr release was unchanged. Evoked release of 3H- ACh and all amino acids except Tyr showed substantial Ca2+ dependence. A significant (p less than 0.05) age-related reduction in both basal (- 35%) and K(+)-stimulated (-42%) efflux of GABA from the CIC was observed. A corresponding decrease in postrelease tissue content of GABA in CIC of aged rats was observed (-30%, p less than 0.05). In contrast, tissue content as well as basal and evoked release of Glu, Asp, Tyr, and 3H-ACh was similar between the 2 age groups. Age-related GABA neurochemical changes described in the CIC were not observed in the release of the other amino acids or 3H-ACh from either the rostral ventrolateral medulla or the somatosensory cortex, 2 brain regions involved in processing non-auditory sensory input. These data support previous findings that GABA, Glu, Asp, and ACh may subserve neurotransmission in the CIC. Additionally, these data provide clear evidence for a pronounced, region- and neurotransmitter-selective, age- related reduction of GABA in the CIC. These findings support the hypothesis that impairment of inhibitory GABAergic neurotransmission in the CIC may contribute to abnormal auditory perception and processing seen in neural presbycusis.

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  • Reduced GABAergic signaling has been demonstrated in the aged auditory system of rodents and humans.

    “several studies have demonstrated reduced GABAergic signaling in the aged auditory system of rodents and humans (Caspary et al., 1990; Ouda et al., 2008; Martin del Campo et al., 2012; Gao et al., 2015).”

    From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Caspary et al., 1990

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  1. Smith PH (1986) Synaptic responses of neurons in brain slices of the guinea pig inferior colliculus. IUPS Satellite Symposium on Hearing, p 82.

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Authors
Caspary, D., Raza, A., Lawhorn Armour, B., Pippin, J., & Arneric, S.
Affiliations
Southern Illinois University Carbondale (US)
ORCID
Pippin, J
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
1990-07-01
Volume
10
Issue
7
Pages
2363-2372
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.10-07-02363.1990
PMC
PMC6570369
OpenAlex
W1937675039
Cited by
235
References
40
Citations by year
2025: 5 · 2024: 5 · 2023: 7 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 10 · 2018: 5 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 14 · 2013: 7 · 2012: 6
FWCI
3.31
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (N01-AG-2104)
  • National Institute on Deafness and Other Communication Disorders (DC00-151)
Topics
  • Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Vestibular and auditory disorders
Keywords
GABA, inferior colliculus, GABAergic neurons, GABA release, glutamate, aspartic acid, acetylcholine, potassium-evoked release, calcium dependence, presynaptic inhibition, auditory brainstem, F344 rats, rostral ventrolateral medulla, somatosensory cortex
MeSH terms
Acetylcholine, Aging, Animals, Aspartic Acid, Calcium, gamma-Aminobutyric Acid, Glutamates, Hearing Loss, Sensorineural, Inferior Colliculi, Neurons, Potassium, Presbycusis, Rats, Inbred F344, Glutamic Acid, Rats

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