RESUMO
In this paper, we introduce a new, open-source software developed in Python for analyzing Auditory Brainstem Response (ABR) waveforms. ABRs are a far-field recording of synchronous neural activity generated by the auditory fibers in the ear in response to sound, and used to study acoustic neural information traveling along the ascending auditory pathway. Common ABR data analysis practices are subject to human interpretation and are labor-intensive, requiring manual annotations and visual estimation of hearing thresholds. The proposed new Auditory Brainstem Response Analyzer (ABRA) software is designed to facilitate the analysis of ABRs by supporting batch data import/export, waveform visualization, and statistical analysis. Techniques implemented in this software include algorithmic peak finding, threshold estimation, latency estimation, time warping for curve alignment, and 3D plotting of ABR waveforms over stimulus frequencies and decibels. The excellent performance on a large dataset of ABR collected from three labs in the field of hearing research that use different experimental recording settings illustrates the efficacy, flexibility, and wide utility of ABRA.
RESUMO
There is considerable interest in whether sensory deficiency is associated with the development of Alzheimer's disease (AD). Notably, the relationship between hearing impairment and AD is of high relevance but still poorly understood. In this study, we found early-onset hearing loss in two AD mouse models, 3xTgAD and 3xTgAD/Polß+/-. The 3xTgAD/Polß+/- mouse is DNA repair deficient and has more humanized AD features than the 3xTgAD. Both AD mouse models showed increased auditory brainstem response (ABR) thresholds between 16 and 32 kHz at 4 weeks of age, much earlier than any AD cognitive and behavioral changes. The ABR thresholds were significantly higher in 3xTgAD/Polß+/- 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.