Early-Onset Hearing Loss in Mouse Models of Alzheimer’s Disease and Increased DNA Damage in the Cochlea
Vilhelm A. Bohr, Jae Hyeon Park, Burcin Duan Sahbaz, Komal Pekhale, Xixia Chu, Mustafa Nazir Okur, M’hamed Grati, Kevin Isgrig, Wade W. Chien, Elena Chrysostomou, L. Sullivan, Deborah L. Croteau, Uri Manor
Abstract
mice than in 3xTgAD mice at 16 kHz, and distortion product otoacoustic emission signals were reduced, indicating that DNA damage may be a factor underlying early hearing impairment in AD. Poly ADP-ribosylation and protein expression levels of DNA damage markers increased significantly in the cochlea of the AD mice but not in the adjacent auditory cortex. Phosphoglycerate mutase 2 levels and the number of synaptic ribbons in the presynaptic zones of inner hair cells were decreased in the cochlea of the AD mice. Furthermore, the activity of sirtuin 3 was downregulated in the cochlea of these mice, indicative of impaired mitochondrial function. Taken together, these findings provide new insights into potential mechanisms for hearing dysfunction in AD and suggest that DNA damage in the cochlea might contribute to the development of early hearing loss in AD.