Source:Hearing Research
Author(s): M.R. Kapolowicz, L.T. Thompson
Tinnitus is a devastating auditory disorder impacting a growing number of people each year. The aims of the current experiment were to assess neuronal mechanisms involved in the initial plasticity after traumatic noise exposure that could contribute to the emergence of tinnitus and to test a potential pharmacological treatment to alter this early neural plasticity. Specifically, this study addressed rapid effects of acute noise trauma on amygdalo-hippocampal circuitry, characterizing biomarkers of both excitation and inhibition in these limbic regions, and compared them to expression of these same markers in primary auditory cortex shortly after acute noise trauma. To assess excitatory plasticity, activity-regulated cytoskeleton-associated (Arc) protein expression was evaluated in male rats 45 min after bilateral exposure to acute high-intensity noise (16 kHz, 115 dB SPL, for 1 hr), sufficient to cause acute cochlear trauma, a common cause of tinnitus in humans and previously shown sufficient to induce tinnitus in rat models of this auditory neuropathology. Western blot analyses confirmed that up-regulation of amygdalo-hippocampal Arc expression occurred rapidly post-noise trauma, corroborating several lines of evidence from our own and other laboratories indicating that limbic brain structures, i.e. outside of the classical auditory pathways, exhibit plasticity early in the initiation of tinnitus. Western blot analyses revealed no noise-induced changes in amygdalo-hippocampal expression of glutamate decarboxylase (GAD), the biosynthetic enzyme required for GABAergic inhibition. No changes in either Arc or GAD protein expression were observed in primary auditory cortex in this immediate post-noise exposure period, confirming other reports that auditory cortical plasticity may not occur until later in the development of tinnitus. As a further control, our experiments compared Arc protein expression between groups exposed to the quiet background of a sound-proof chamber to those exposed not only to the traumatic noise described above, but also to an intermediate, non-traumatic noise level (70 dB SPL) for the same duration in each of these three brain regions. We found that non-traumatic noise did not up-regulate Arc protein expression in these brain regions. To see if changes in Arc expression due to acute traumatic noise exposure were stress-related, we compared circulating serum corticosterone in controls and rats exposed to traumatic noise at the time when changes in Arc were observed, and found no significant differences in this stress hormone in our experimental conditions. Finally, the ability of D-cycloserine (DCS; an NMDA-receptor NR1 partial agonist) to reduce or prevent the noise trauma-related plastic changes in the biomarker, Arc, was tested. D-cycloserine prevented traumatic noise-induced up-regulation of Arc protein expression in amygdala but not in hippocampus, suggesting that DCS alone is not fully effective in eliminating regionally-specific early plastic changes after traumatic noise exposure.
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