Gene Expression Patterns in Functionally Different Cochlear Compartments of the Newborn Rat

Abstract

<p class="1Body">In an experimental model of organotypic cultures of the stria vascularis (SV), the organ of Corti (OC) and the modiolus (MOD), we compared the expression levels and injury/hypoxia induced response of 36 genes associated with the cells´ energy-producing and energy-consuming processes, using the microarray technique. A decrease of expression was observed for most of the voltage-dependent K⁺- and Ca⁺⁺- channels as an effective mechanism to lower energetic demands. We identified two gene networks of transcripts that are differentially expressed across the three regions. One cluster is associated with the transcription factor hypoxia-inducing factor (<em>Hif-1a</em>) and the second one with the caspase and calpain cell death genes <em>Casp3, Capn1, Capn2</em> and <em>Capns1</em>. The <em>Hif-1a</em> gene subset consists of genes belonging to the glucose metabolism (glucose transporter <em>Slc2a1</em>, glycolytic enzymes <em>Gapdh</em>, <em>Hk1</em> and <em>Eno2</em>), the Na⁺/K⁺ homeostasis (ATPase <em>Atp1a1</em>) and the glutamate pathway (NMDA receptor associated protein 1 <em>Grina</em>, glutamate transporter <em>Slc1a1</em>, <em>Slc1a3</em>). The <em>Slc2a1</em>, <em>Gapdh</em>, <em>Hk1</em>, <em>Slc1a3</em>, <em>Grina</em> and <em>Atp1a1</em> transcripts are also members of the cell death subset indicating a role they have to play in the differential regional cell death rates. The newly identified genes <em>Grina</em> and calnexin (<em>Canx</em>) may play specific and yet unknown roles in regulating cell death induced by injury and hypoxia in the inner ear. We assume that the differential regional response occurs on the basis of endogenous gene regulatory mechanisms and may be important to maintaining the cochlea’s function following damage from trauma and hypoxia.</p>