MORPHOLOGICAL PHENOTYPING OF THE MOUSE AGING COCLEA: LINKING BASIC RESEARCH TO PRECLINICAL APPLICATIONS

Morphological mouse phenotyping plays a pivotal role in the translational setting by providing a reliable framework for molecular and instrumental an alysis and this is even more accurate in the arena of auditory research, where mouse is a central model organism due to a high degree of evolutionary genetic relationship and morpho functional analogies with the human auditory system (1). In this work, we approach the characterization of aging process in mouse cochlea by comparing significant morphological markers in mice belonging to two of the most common used inbred (C57BL/6) and outbred (CD1) strains in both male and females during aging, i.e. in anima ls ranging from 2 to 18 months of age (approved by Ministry of Health with protocol 1177/2020 PR). Further, we strive to integrate morphological data with those stemming from molecular and instrumental analyses (auditory brainstem response) to correlate mo rphological changes to transcriptional variation and functional discrepancies between both strains and sexes (2). At each timepoint, we stained the tissue by haematoxyilin eosin to highlight morphological changes and identified by immunofluorescence key mo lecules in signal transduction to detect at which stage the sensory decline starts and, therefore, track the degenerative process. Specifically, to identify age related neurodegeneration indicators, we featured the localization of TMC1, Gipc3, Myosin VIIa, and Cdh23 in the hair cells. Further to gain more insights on the correlation between synaptopathy and sensory hair cell loss we labeled NF200 which identifies neural cytoskeleton. Over aging, we observed a clear drop in the selected marker occurrence and in the number of type 1 spiral ganglion neurons which are the first action potential generating neurons in the auditory pathway (3). Notably, our observations were performed in inbred and outbred mouse strains which may be an asset to investigate the phys iological trigger of age related hearing loss. In addition, this study is part of a broader project that includes the characterization of vision loss at the same timepoints to identify the potential onset of compensatory mechanisms between the two senses ( 4). Overall, our data may provide new insights in the translational setting as well as in comparing the phenotypic variation in the two most common used laboratory mouse strains (2).