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

Abstract

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 (Hif-1a) and the second one with the caspase and calpain cell death genes Casp3, Capn1, Capn2 and Capns1. The Hif-1a gene subset consists of genes belonging to the glucose metabolism (glucose transporter Slc2a1, glycolytic enzymes Gapdh, Hk1 and Eno2), the Na + /K + homeostasis (ATPase Atp1a1) and the glutamate pathway (NMDA receptor associated protein 1 Grina, glutamate transporter Slc1a1, Slc1a3). The Slc2a1, Gapdh, Hk1, Slc1a3, Grina and Atp1a1 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 Grina and calnexin (Canx) 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.

Comparative assessment of Fgf's diverse roles in inner ear development: A zebrafish perspective

“…Thus, the shift to aerobic glycolysis and lactate signaling helps "jump start" Fgf-dependent activation of neural and sensory development. Gene expression data suggest that aerobic glycolysis may occur in the cochlea of chick and rat as well, 92,93 although relevant functional studies have not yet been reported.…”

Expression of nestin-associated genes in the inner ear of newborn rats following injury and hypoxia

“…1B). Remarkably, these cell death patterns are associated with two gene coexpression clusters, a cluster around Hif-1a (hypoxia inducible factor -1alpha), the key transcription factor that regulates adaptation to hypoxia [6] , and a cluster around several cell-death-associated transcripts that include, among other genes, the ROS-associated molecules Sod3, the inflammatory chemokine Ccl20, the glutamate associated NMDA receptor-associated complex protein NMDARA1 Grina and the glutamate transporter Slc1a3 [4,7] .…”

“…Pcp4 encodes for the small brain-specific protein Purkinje cell protein 4. We assume that the early response of Gap43 [4,7] .…”