Reduction of Behavioral Manifestation of Tinnitus Through the Utilization of BK Channel Opener
Mentor Information
Joseph Walton (Department of Communication Sciences and Disorders)
Description
Tinnitus, or “ringing in the ears”, is a prevalent hearing disorder. This study evaluates the effect of the drug candidate, CS0022, on the behavior of male CBA/CaJ mice with acoustic trauma (AT)-induced tinnitus. This compound is known to target the large-conductance calcium and voltage-activated potassium channel, or BK channel. This channel regulates neuronal excitability in the peripheral and central nervous system. Our hypothesis is that positive modulation of BK channel function mitigates changes in central auditory system activity that support the tinnitus percept. Behavioral evidence of tinnitus in mice models can be assessed through the quantification of the acoustic startle reflex and prepulse inhibition. This study used Gap-Prepulse-Inhibition of the Acoustic Startle Response (GPIAS) to determine the presence and extent of tinnitus in the subjects. The GPIAS assay was first conducted on each mouse for baseline readings prior to AT with a 16 kHz narrowband noise. Post-AT behavioral assessments were conducted 7 to 9 weeks after trauma to select mice that developed tinnitus, while effect was assessed 10 to 11 weeks after trauma. Consecutively, Auditory Brainstem Responses (ABR) were collected to determine hearing thresholds of the subjects and helped evaluate the severity of threshold shifts. The findings suggest that treatment with CS0022 can improve AT-induced tinnitus in mice by modifying BK channels. The GPIAS results were statistically analyzed using a computational approach called Gstar. The ongoing analysis will focus on determining the relationship between the presence of tinnitus and the influence of treatment on permanent hearing loss.
Reduction of Behavioral Manifestation of Tinnitus Through the Utilization of BK Channel Opener
Tinnitus, or “ringing in the ears”, is a prevalent hearing disorder. This study evaluates the effect of the drug candidate, CS0022, on the behavior of male CBA/CaJ mice with acoustic trauma (AT)-induced tinnitus. This compound is known to target the large-conductance calcium and voltage-activated potassium channel, or BK channel. This channel regulates neuronal excitability in the peripheral and central nervous system. Our hypothesis is that positive modulation of BK channel function mitigates changes in central auditory system activity that support the tinnitus percept. Behavioral evidence of tinnitus in mice models can be assessed through the quantification of the acoustic startle reflex and prepulse inhibition. This study used Gap-Prepulse-Inhibition of the Acoustic Startle Response (GPIAS) to determine the presence and extent of tinnitus in the subjects. The GPIAS assay was first conducted on each mouse for baseline readings prior to AT with a 16 kHz narrowband noise. Post-AT behavioral assessments were conducted 7 to 9 weeks after trauma to select mice that developed tinnitus, while effect was assessed 10 to 11 weeks after trauma. Consecutively, Auditory Brainstem Responses (ABR) were collected to determine hearing thresholds of the subjects and helped evaluate the severity of threshold shifts. The findings suggest that treatment with CS0022 can improve AT-induced tinnitus in mice by modifying BK channels. The GPIAS results were statistically analyzed using a computational approach called Gstar. The ongoing analysis will focus on determining the relationship between the presence of tinnitus and the influence of treatment on permanent hearing loss.
