Molecular profile of vestibular compensation in the medial vestibular nucleus after unilateral labyrinthectomy

Abstract

Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in the central nervous system, yet their role in vestibular compensation remains elusive. To address this knowledge gap, we employed unilateral labyrinthectomy (UL) in rats to establish animal models of peripheral vestibular dysfunction. Utilizing ribonucleic acid sequencing (RNA-seq), we comprehensively analysed the expression profiles of genes dysregulated in the medial vestibular nucleus (MVN) of these rats at distinct time points: 4 h, 4 days, and 14 days post-UL. Through trans-target prediction analysis integrating differentially co-expressed messenger RNAs (mRNAs) and lncRNAs, we constructed lncRNA-mRNA regulatory networks. Validation of selected mRNAs and lncRNAs was performed using RT-qPCR. Our RNA-seq analysis revealed significant aberrant expression of 3054 lncRNAs and 1135 mRNAs compared to control samples. By applying weighted gene co-expression network analysis (WGCNA), we identified 11 co-expressed modules encompassing all genes. Notably, within the MEmagenta module, we observed an initial upregulation of differentially expressed genes (DEGs) at 4 h, followed by downregulation at 4- and 14-days post-UL. Our findings indicated that 3068 lncRNAs positively regulated 1259 DEGs, while 1482 lncRNAs negatively regulated 433 DEGs in the MVN. The RT-qPCR results corroborated the RNA-seq data, validating our findings. This study offers novel insights into the lncRNA-mRNA expression landscape during vestibular compensation, paving the way for further exploration of lncRNA functions in this context.

Keywords: lncRNAs; medial vestibular nucleus; unilateral labyrinthectomy; vestibular compensation.