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Cellular and Molecular Neurobiology

, Volume 34, Issue 4, pp 523–538 | Cite as

Differential Expression of Transcription Factors and Inflammation-, ROS-, and Cell Death-Related Genes in Organotypic Cultures in the Modiolus, the Organ of Corti and the Stria Vascularis of Newborn Rats

  • Johann Gross
  • Heidi Olze
  • Birgit Mazurek
Original Research

Abstract

Cells respond to injury and hypoxia by changing gene expression. To study how the main compartments of the cochlea, the stria vascularis (SV), the organ of Corti (OC), and the modiolus (MOD), respond to such stress, we analyzed the expression of selected genes using microarray analysis. Organotypic cultures of SV, OC, and MOD from newborn rats were used as an experimental model. In the present study, we compare the expression of a total of 50 genes involved in apoptosis and necrosis, reactive oxygen species (ROS) metabolism, inflammation as well as selected transcription factors (TF) and analyze their role for the different cell death patterns observed in the three regions. MOD, OC, and SV differ not only in their basal gene profiles but also in their ability to respond to injury and hypoxia. The results provide two coexpression clusters across the three regions, a Hif-1a coexpression cluster and a cluster around the cell death-associated transcripts Casp3, Capn1, Capn2, and Capns1. These clusters include the TF Jun, Bmyc, Nfyc, Foxd3, Hes1, the ROS-associated molecules Sod3, and Nos2, and the inflammatory chemokine Ccl20. The evidence of both clusters indicates the complex and regulated character of gene expression following injury and hypoxia across the three regions SV, OC, and MOD. The high vulnerability of spiral ganglion neurons in the MOD region, previously explained on the basis of the availability of neuro-trophic factors, is associated with the increased endogenous production of ROS and nitric oxide and inadequate activation of protective acting genes.

Keywords

Cell death Culture Gene expression Hypoxia Inflammation Inner ear Microarray Modiolus Organ of Corti Reactive oxygen species Spiral ganglion neurons Stria vascularis 

Notes

Acknowledgments

We would like to thank the University Hospital Charité for support. It gives us great pleasure to thank Johannes Wendt for his generous help in critically reading and correcting this article.

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Molecular Biology Research Laboratory, Department of OtorhinolaryngologyCharité-Universitätsmedizin BerlinBerlinGermany
  2. 2.Department of OtorhinolaryngologyCharité-Universitätsmedizin BerlinBerlinGermany

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