Long-Term Neurochemical Changes within the Cochlear Nucleus and the Auditory Cortex in Acoustic Trauma-Induced Tinnitus Rats
Tinnitus is a debilitating auditory disorder commonly described as a ringing in the ears in the absence of a physical external sound source. Although a variety of risk factors has been reported to be related to the perception of tinnitus, sound overexposure is considered the main cause. Neuronal hyperactivity is one of the potential mechanisms for the genesis of tinnitus and has been found within major regions in the central auditory system, including the cochlear nucleus (CN) and the auditory cortex (AC). The hyperactivity of neurons has been correlated to the imbalance of excitation and inhibition caused by neurotransmitter alterations, amino acids in particular. However, there is no study that directly correlated acoustic trauma and/or tinnitus with extracellular levels of amino acids, which are more accurate measurements in reflecting the functions of those neurochemicals. Theref ore, the present study aimed to investigate how the extracellular amino acid levels altered in the CN and the AC in rats with tinnitus using the in vivo microdialysis technique. The effects of sound stimulation on amino acid changes in the two regions were also examined. In addition, the effect of age on neurochemical changes associated with tinnitus was also examined, owing to the 2-month age gap caused by the COVID-19 lockdown. The animals were exposed to 1-h unilateral acoustic trauma at 16 kHz, 110 dB SPL under anaesthesia and hearing levels were measured before, immediately and about 5 months after acoustic trauma. The animals were tested 5 weeks post-exposure to confirm the development of tinnitus using the conditioned lick-suppression paradigm. Following the confirmation of tinnitus, in vivo microdialysis was combined with high-performance liquid chromatography (HPLC) to measure the extracellular concentrations of amino acids. An immediate hearing loss was evident in the exposed ear of rats following acoustic trauma (P ≤ 0.001) and 70% of exposed rats were confirmed to exhibit tinnitus-like behaviour at 5 weeks after acoustic trauma. The hearing levels were tested again at 5 months after acoustic trauma and they were completely recovered in all of the old rats and 7 out of the 10 young rats. However, hearing levels were partially recovered in 3 out of the 10 young rats. There was no significant difference on either the basal amino acid levels or the sound stimulation evoked amino acid changes between sham and exposed rats or between sham and tinnitus rats in the CN and the AC. It was found that amino acid levels between sound stimulation and silent periods varied significantly for threonine, taurine and alanine in the CN and glutamine, serine and taurine in the AC. Furthermore, there were also age-related changes in the basal and/or sound-evoked amino acid levels for glutamate, threonine and serine. These results suggest that acoustic trauma and/or tinnitus did not cause long-term changes in the extracellular concentrations of amino acids, which provided a new line of evidence for a better understanding of the neurochemical mechanisms of tinnitus. The study also demonstrated that extracellular concentrations of amino acids could be altered by age and sound stimulations, which provided some preliminary evidence for further investigation into the neurochemical shaping of neuronal response to sound or aging.
Advisor: Zheng, Yiwen; Smith, Paul
Degree Name: Master of Science
Degree Discipline: Pharmacology and Toxicology
Publisher: University of Otago
Keywords: Tinnitus; neurotransmitters
Research Type: Thesis