Transcriptome Analysis of Deafness: Intracellular Signal Transduction Signaling Pathways Regulate Neuroplastic Changes in the Auditory Cortex

Hypothesis and Background: Hearing loss leads to synaptic changes in auditory neurons and their networks, and functions as a consequence of the interplay between genes and proteins. However, cellular and molecular mechanisms leading to deafness-induced plasticity in the auditory cortex (AC) remain unclear. Here, we examined the changes in gene expression and key signaling pathways that regulate differentially expressed genes (DEGs) in the AC following auditory deafferentation using RNA-sequencing (RNA-Seq) analysis. Methods: Cochlear ablation-induced bilaterally deafened Sprague-Dawley rats were maintained for 12 weeks and their ACs were harvested. RNA-seq analysis was performed on each sample to identify which genes were expressed. This information was then used for comparative analysis of DEGs between samples. The statistical significance of DEGs was determined by fold change (vertical bar FC vertical bar> 1.5) and independent t test (p<0.05). Results: RNA-seq analysis identified 72 DEGs, of which 19 were upregulated and 53 were down-regulated after bilateral deafening in the ACs. Gene ontology (GO) analysis revealed the potential involvement of mitogen-activated protein kinase, tumor necrosis factor, and cyclic adenosine 3',5'-monophosphate (e.g., Bdnf, Gli1, and c-Fos) signaling pathways in regulating changes in the expression of the genes listed herein. The DEGs of interest-including c-Fos, Arc, Ntf3, and Gli1-from the RNA-seq analysis were consistent with result of quantitative reverse transcriptase polymerase chain reaction. Conclusion: RNA-seq analysis revealed that auditory deprivation in adult rats elicited changes in gene expression, transcription factor levels, and their complex interaction at specific gene promoters in the AC. Particularly, activation of intracellular signal transduction signaling pathways may be key to neuronal plasticity in deafness.