Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Research Abstract |
Sphingomyelin (SM) is a sphingolipid reported to function as astructural component of plasma membranes and to participate in signal transduction.The role of SM metabolism in the process of hearing remains controversial. Here, weexamined the role of SM synthase (SMS), which is subcategorized into the familymembers SMS1 and SMS2, in auditory function. Measurements of auditory brainstemresponse (ABR) revealed hearing impairment in SMS1-/-mice in a low frequency range(4-16 kHz). As a possible mechanism of this impairment, we found that the striavascularis (SV) in these mice exhibited atrophy and disorganized marginal cells.Consequently , SMS1-/-mice exhibited significantly smaller endocochlear potentials(EPs). As a possible mechanism for EP reduction, we found altered expression patternsand a reduced level of KCNQ1 channel protein in the SV of SMS1-/-mice. These micealso exhibited reduced levels of distortion product otoacoustic emissions. Quantitativecomparison of the SV atrophy , KCNQ1 expression, and outer hair cell density at thecochlear apical and basal turns revealed no location-dependence, but more macrophageinvasion into the SV was observed in the apical region than the basal region,suggesting a role of cochlear location-dependent oxidative stress in producing thefrequency-dependence of hearing loss in SMS1-/-mice. Elevated ABR thresholds,decreased EPs, and abnormal KCNQ1 expression patterns in SMS1-/-mice were allfound to be progressive with age. Mice lacking SMS2, however , exhibited neitherdetectable hearing loss nor changes in their EPs. Taken together , our results suggestthat hearing impairments occur in SMS1-/-but not SMS2-/-mice. Defects in the SV withsubsequent reductions in EPs may account, at least partially , for hearing impairmentsin SMS1-/-mice.
|