Lack of Amino Acid Alterations within the Cochlear Nucleus and the Auditory Cortex in Acoustic Trauma-Induced Tinnitus Rats using In Vivo Microdialysis

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Abstract

Tinnitus is a debilitating auditory disorder commonly described as a ringing in the ears in the absence of an external sound source. Although various risk factors have been reported to be related to the perception of tinnitus, sound trauma is considered the primary cause. Neuronal hyperactivity is one of the potential mechanisms for the genesis of tinnitus and has been identified within major regions of the central auditory system, including the cochlear nucleus (CN) and the auditory cortex (AC). An imbalance of excitatory and inhibitory neu-rotransmission has been attributed to this hyperactivity. However, no study has directly cor-related tinnitus with the extracellular levels of amino acids in the CN and the AC using mi-crodialysis, which reflects the functions of these neurochemicals. In the present study, rats were exposed to either a sham condition or acoustic trauma and then subjected to behavioral confirmation of tinnitus after one month. They were further divided into sham (aged n=6; young n=6), tinnitus-positive (aged n=7; young n=7), and tinnitus-negative (aged n=3; young n=3) groups. In vivo microdialysis was utilized to collect samples from the CN and the AC simultaneously in the same rat. Extracellular levels of amino acids were quantified using high-performance liquid chromatography (HPLC) coupled with an electrochemical detector (ECD). The effects of sound stimulation and age on neurochemical changes associ-ated with tinnitus were also examined. It was found that there were no significant differ-ences in either the basal levels or the sound stimulation-evoked changes of any of the amino acids examined in the CN and the AC, between sham and tinnitus animals. However, the ba-sal levels of serine and threonine exhibited age-related alterations in the AC and significant differences in threonine and glycine levels were observed in the responses to 4 kHz and 16 kHz stimuli in the CN. These results demonstrated a lack of a direct link between extracellu-lar levels of amino acids in the CN and the AC and tinnitus perception in a rat model of tin-nitus. Further studies investigating a wide range of neurochemicals in both auditory and non-auditory brain regions are needed in order to understand tinnitus-related changes in neuro-transmission.

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