Limits...
Gamma-aminobutyric acid and glutamic acid levels in the auditory pathway of rats with chronic tinnitus: a direct determination using high resolution point-resolved proton magnetic resonance spectroscopy (H-MRS).

Brozoski T, Odintsov B, Bauer C - Front Syst Neurosci (2012)

Bottom Line: Decreased GABA levels were evident only in the MGB, with the greatest decrease, relative to unexposed controls, obtained in the contralateral MGB.In the MGB Glu was increased ipsilaterally but decreased contralaterally.The present results also suggest that targeting both neurotransmitter systems may be optimal in developing more effective therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Division of Otolaryngology, Southern Illinois University School of Medicine, Springfield IL, USA.

ABSTRACT
Damage to the auditory system following high-level sound exposure reduces afferent input. Homeostatic mechanisms appear to compensate for the loss. Overcompensation may produce the sensation of sound without an objective physical correlate, i.e., tinnitus. Several potential compensatory neural processes have been identified, such as increased spontaneous activity. The cellular mechanisms enabling such compensatory processes may involve down-regulation of inhibitory neurotransmission mediated by γ-amino butyric acid (GABA), and/or up-regulation of excitatory neurotransmission, mediated by glutamic acid (Glu). Because central processing systems are integrated and well-regulated, compensatory changes in one system may produce reactive changes in others. Some or all may be relevant to tinnitus. To examine the roles of GABA and Glu in tinnitus, high resolution point-resolved proton magnetic resonance spectroscopy ((1)H-MRS) was used to quantify their levels in the dorsal cochlear nucleus (DCN), inferior colliculus (IC), medial geniculate body (MGB), and primary auditory cortex (A1) of rats. Chronic tinnitus was produced by a single high-level unilateral exposure to noise, and was measured using a psychophysical procedure sensitive to tinnitus. Decreased GABA levels were evident only in the MGB, with the greatest decrease, relative to unexposed controls, obtained in the contralateral MGB. Small GABA increases may have been present bilaterally in A1 and in the contralateral DCN. Although Glu levels showed considerable variation, Glu was moderately and bilaterally elevated both in the DCN and in A1. In the MGB Glu was increased ipsilaterally but decreased contralaterally. These bidirectional and region-specific alterations in GABA and Glu may reflect large-scale changes in inhibitory and excitatory equilibrium accompanying chronic tinnitus. The present results also suggest that targeting both neurotransmitter systems may be optimal in developing more effective therapeutics.

No MeSH data available.


Related in: MedlinePlus

Auditory brainstem response thresholds for exposed and unexposed rats. Top panel: thresholds before and immediately after acoustic exposure. Significant threshold elevation was evident only in the exposed ear. Bottom panel: thresholds prior to spectroscopy show normal levels in both groups. Error bars show the standard error of the mean.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3285819&req=5

Figure 9: Auditory brainstem response thresholds for exposed and unexposed rats. Top panel: thresholds before and immediately after acoustic exposure. Significant threshold elevation was evident only in the exposed ear. Bottom panel: thresholds prior to spectroscopy show normal levels in both groups. Error bars show the standard error of the mean.

Mentions: The sound exposure used to produce tinnitus was unilateral. This was done to preserve free-field hearing thresholds, a requirement for psychophysical testing. Immediately after exposure (peak sound level at 116 dB, SPL), exposed ear hearing thresholds, as indicated by ABR, were elevated approximately 60 dB at 20 kHz (Figure 9, top panel). Thresholds for unexposed ears were not affected by the exposure. At the conclusion of psychophysical testing, and prior to MRS data collection, ABR thresholds for exposed ears returned to normal levels (Figure 9, bottom panel). Recovery of threshold sensitivity is typical for this level of exposure (Bauer and Brozoski, 2001) in Long Evans rats.


Gamma-aminobutyric acid and glutamic acid levels in the auditory pathway of rats with chronic tinnitus: a direct determination using high resolution point-resolved proton magnetic resonance spectroscopy (H-MRS).

Brozoski T, Odintsov B, Bauer C - Front Syst Neurosci (2012)

Auditory brainstem response thresholds for exposed and unexposed rats. Top panel: thresholds before and immediately after acoustic exposure. Significant threshold elevation was evident only in the exposed ear. Bottom panel: thresholds prior to spectroscopy show normal levels in both groups. Error bars show the standard error of the mean.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3285819&req=5

Figure 9: Auditory brainstem response thresholds for exposed and unexposed rats. Top panel: thresholds before and immediately after acoustic exposure. Significant threshold elevation was evident only in the exposed ear. Bottom panel: thresholds prior to spectroscopy show normal levels in both groups. Error bars show the standard error of the mean.
Mentions: The sound exposure used to produce tinnitus was unilateral. This was done to preserve free-field hearing thresholds, a requirement for psychophysical testing. Immediately after exposure (peak sound level at 116 dB, SPL), exposed ear hearing thresholds, as indicated by ABR, were elevated approximately 60 dB at 20 kHz (Figure 9, top panel). Thresholds for unexposed ears were not affected by the exposure. At the conclusion of psychophysical testing, and prior to MRS data collection, ABR thresholds for exposed ears returned to normal levels (Figure 9, bottom panel). Recovery of threshold sensitivity is typical for this level of exposure (Bauer and Brozoski, 2001) in Long Evans rats.

Bottom Line: Decreased GABA levels were evident only in the MGB, with the greatest decrease, relative to unexposed controls, obtained in the contralateral MGB.In the MGB Glu was increased ipsilaterally but decreased contralaterally.The present results also suggest that targeting both neurotransmitter systems may be optimal in developing more effective therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Division of Otolaryngology, Southern Illinois University School of Medicine, Springfield IL, USA.

ABSTRACT
Damage to the auditory system following high-level sound exposure reduces afferent input. Homeostatic mechanisms appear to compensate for the loss. Overcompensation may produce the sensation of sound without an objective physical correlate, i.e., tinnitus. Several potential compensatory neural processes have been identified, such as increased spontaneous activity. The cellular mechanisms enabling such compensatory processes may involve down-regulation of inhibitory neurotransmission mediated by γ-amino butyric acid (GABA), and/or up-regulation of excitatory neurotransmission, mediated by glutamic acid (Glu). Because central processing systems are integrated and well-regulated, compensatory changes in one system may produce reactive changes in others. Some or all may be relevant to tinnitus. To examine the roles of GABA and Glu in tinnitus, high resolution point-resolved proton magnetic resonance spectroscopy ((1)H-MRS) was used to quantify their levels in the dorsal cochlear nucleus (DCN), inferior colliculus (IC), medial geniculate body (MGB), and primary auditory cortex (A1) of rats. Chronic tinnitus was produced by a single high-level unilateral exposure to noise, and was measured using a psychophysical procedure sensitive to tinnitus. Decreased GABA levels were evident only in the MGB, with the greatest decrease, relative to unexposed controls, obtained in the contralateral MGB. Small GABA increases may have been present bilaterally in A1 and in the contralateral DCN. Although Glu levels showed considerable variation, Glu was moderately and bilaterally elevated both in the DCN and in A1. In the MGB Glu was increased ipsilaterally but decreased contralaterally. These bidirectional and region-specific alterations in GABA and Glu may reflect large-scale changes in inhibitory and excitatory equilibrium accompanying chronic tinnitus. The present results also suggest that targeting both neurotransmitter systems may be optimal in developing more effective therapeutics.

No MeSH data available.


Related in: MedlinePlus