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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

Calibration of GABA spectra using an array of phantoms, each containing 10 mM GABA in sterile normal saline, distributed across the imaging field of view. Using multiple phantoms arrayed throughout the field of view illustrates optimized field shimming and selection of the least-variant spectral peak, from among the multiplets at each location, used to quantify the compound of interest (in this example, GABA).
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Figure 1: Calibration of GABA spectra using an array of phantoms, each containing 10 mM GABA in sterile normal saline, distributed across the imaging field of view. Using multiple phantoms arrayed throughout the field of view illustrates optimized field shimming and selection of the least-variant spectral peak, from among the multiplets at each location, used to quantify the compound of interest (in this example, GABA).

Mentions: Prior to spectrum acquisition, glass vessels 2 mm in diameter were prepared with either 10 mM of GABA or 10 mM of Glu dissolved in sterile normal saline. Initial attempts to include one or more calibration vessels along with the brain during spectrographic data acquisition distorted the field, making shimming impossible. Therefore, calibration spectra were obtained either before or after acquisition of brain spectra. Initial calibrations were done with GABA and Glu in combination with compounds, such as creatine, that were expected to produce unwanted spectral lines potentially obscuring those of GABA and Glu. Spectrograms of the mixtures were used to identify GABA and Glu peaks, from among their multiplets, that provided the clearest separation from background. Calibration and peak selection were further refined using arrays of phantoms distributed in the field of view as shown in Figure 1. Taking into account all calibration results, GABA levels were determined using the peak at 2.18 ppm and Glu using the peak at 3.68 ppm (Figure 2).


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)

Calibration of GABA spectra using an array of phantoms, each containing 10 mM GABA in sterile normal saline, distributed across the imaging field of view. Using multiple phantoms arrayed throughout the field of view illustrates optimized field shimming and selection of the least-variant spectral peak, from among the multiplets at each location, used to quantify the compound of interest (in this example, GABA).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Calibration of GABA spectra using an array of phantoms, each containing 10 mM GABA in sterile normal saline, distributed across the imaging field of view. Using multiple phantoms arrayed throughout the field of view illustrates optimized field shimming and selection of the least-variant spectral peak, from among the multiplets at each location, used to quantify the compound of interest (in this example, GABA).
Mentions: Prior to spectrum acquisition, glass vessels 2 mm in diameter were prepared with either 10 mM of GABA or 10 mM of Glu dissolved in sterile normal saline. Initial attempts to include one or more calibration vessels along with the brain during spectrographic data acquisition distorted the field, making shimming impossible. Therefore, calibration spectra were obtained either before or after acquisition of brain spectra. Initial calibrations were done with GABA and Glu in combination with compounds, such as creatine, that were expected to produce unwanted spectral lines potentially obscuring those of GABA and Glu. Spectrograms of the mixtures were used to identify GABA and Glu peaks, from among their multiplets, that provided the clearest separation from background. Calibration and peak selection were further refined using arrays of phantoms distributed in the field of view as shown in Figure 1. Taking into account all calibration results, GABA levels were determined using the peak at 2.18 ppm and Glu using the peak at 3.68 ppm (Figure 2).

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