Research Project
10288729
Current Abstract - Supplement Recent data suggest an association between Alzheimer?s disease and hearing loss. Some reports suggest that amyloid ? (A?) deposition in the cochlea could account for the hearing loss. In transgenic mouse models of Alzheimer?s disease, it has been shown that the loss of hearing was associated with A? deposition in the cochlea. Previous studies from our laboratory indicate that A? increases Ca2+ and increased inflammatory markers in primary neuron cultures from rats. In addition, we observed that cortical tissues from 3xTg mouse model (also known as 3xTg-AD model) have increased levels of TNF-?. We speculate that a similar event occurs in the cochleae of Alzheimer?s disease mouse models which could contribute to hearing loss in these mice. Since our current RO1 proposal is based on the hypothesis that cochlear inflammation produces hearing loss, we believe that a Supplement on Alzheimer?s disease is within the general scope of the original grant. Therefore, experiments outlined in the supplement will test the hypothesis that Alzheimer?s transgenic mice show a time- dependent loss of hearing which is associated with A? accumulation in the cochlea. Specific aim 1 will explore the age-dependent loss of hearing in the 5XFAD mouse model covering the postnatal period 0 to 6 months during which these mice show amyloid deposition in the brain and cognitive deficits. Various inflammatory and apoptotic markers will be examined by immunohistochemical and real time PCR assays. Specific aim 2 will examine the effect of oral epigallocatechin gallate (EGCG), a natural product with antioxidant and anti- inflammatory properties, on the development of hearing loss in this mouse model. This drug shows promise for treatment of Alzheimer?s disease in preclinical trials. EGCG is currently being used in the current parent RO1 to treat cisplatin ototoxicity. It was shown to particularly effective for this indication. We believe this product stands a good chance in providing hearing protection in these animals and ultimately in humans suffering from Alzheimer?s-induced hearing loss.
