Transcriptomic analysis highlights cochlear inflammation associated with age-related hearing loss in C57BL/6 mice using next generation sequencing

Background In our aging society, age-related hearing loss (AHL) is the most common sensory disorder in old people. Much progress has been made in understanding the pathological process of AHL over the past few decades. However, the mechanism of cochlear degeneration during aging is still not fully understood. Methods Next generation sequencing technique was used to sequence the whole transcriptome of the cochlea of C57BL/6 mice, a mouse model of AHL. Differentially expressed genes (DEGs) were identified using the Cuffdiff software. GO and KEGG pathway enrichment analyses of the DEGs were implemented by using the GOseq R package and KOBAS software, respectively. Results A total of 731 genes (379 up- and 352 down-regulated) were revealed to be differentially expressed in the cochlea of aged mice compared to the young. Many genes associated with aging, apoptosis, necroptosis and particularly, inflammation were identified as being significantly modulated in the aged cochlea. GO and KEGG analyses of the upregulated DEGs revealed that the most enriched terms were associated with immune responses and inflammatory pathways, whereas many of the downregulated genes are involved in ion channel function and neuronal signaling. Real-time qPCR showed that H2O2 treatment significantly induced the expression of multiple inflammation and necroptosis-related genes in HEI-OC1 cells. Conclusion Using next generation sequencing, our transcriptomic analysis revealed the differences of gene expression pattern with age in the cochlea of C57BL/6 mice. Our study also revealed multiple immune and inflammatory transcriptomic changes during cochlear aging and provides new insights into the molecular mechanisms underlying cochlear inflammation in AHL.

Neurosyphilis and classical music: the great composers and “The Great Imitator”

ABSTRACT Throughout history, neurosyphilis has victimized many people, including classical composers, with a wide range of clinical presentations. Methods: Six articles with descriptions of composers with possible neurosyphilis were reviewed. Results: Neurosyphilis is a possible diagnosis for composers like Beethoven, whose progressive hearing loss influenced his career, culminating in complete deafness. In his autopsy, cochlear nerve atrophy and cochlear inflammation were described. Donizetti developed behavioral changes, as well as headaches, general paresis and seizures. Both Schumann and Wolf suffered from personality changes, persecutory delusions and general paresis. Joplin and Delius also had symptoms attributed to syphilis. Autopsy findings confirmed the diagnosis of Smetana, who developed dementia, deafness and auditory hallucinations with rapid progression. His tinnitus was musically represented in his first String Quartet. Conclusion: Neurosyphilis victimized several notorious composers. It can be argued that neurosyphilis was a major source of inspiration as well, being responsible for the genesis of musical masterpieces.

Postnatal Development of Microglia-Like Cells in Mouse Cochlea

Microglial cells are involved in surveillance and cleaning of the central nervous system. Recently, microglial-like cells (MLC) have been found in an adult cochlea and investigated for their role in cochlear inflammation. The presence and potential roles of MLCs during the development of the cochlea, however, remain unclear. In this study, immunostaining was performed using the MLC-specific marker IBA1 to characterize the presence, distribution, and morphology of MLCs in the developing cochlea. From P0 to P14, MLCs were present in a variety of cochlear regions including the modiolus, spiral lamina, spiral ganglion, spiral ligament, and the organ of Corti. Interestingly, the overall number of MLCs in a mouse cochlea steadily increased since P0, peaks at P5, then gradually decreased from P5 to P14. In the spiral ligament, the distribution of the MLCs trends to shift from the type I/II fibrocyte-rich regions to the type III/IV fibrocyte-rich regions during the course of cochlear development, accompanied by the morphological changes of MLCs from the amoeboid, activated form to the ramified, quiescent form. Our results suggested that MLCs experience drastic morphological and distributional changes during postnatal cochlear development, which may play a role in the maturing and remodeling of the cochlea.