gms | German Medical Science

Introduction: Sensorineural hearing loss is associated with loss of the hair cells in the cochlea. By the common hypothesis, cell death provoked by deafferentation of neurons may reflect deprivation of the neurotrophic factors. In this project signalling of neurotrophic factors in the context of apoptotic mechanisms in the auditory nerve (AN) by gene expression analysis following 7, 14, and 28 days deafening is determined.

Methods: Differential gene expression of BDNF and GDNF, their receptors trkB, p75NTR and GFRα1, the pro-apoptotic signal molecules caspase 9, Bax and anti-apoptotic signal molecules GLAST, Bcl-2 are being studied within this time interval by real time-PCR. For that total RNA was extracted from the AN of 20 normal and deafened animal, respectively, sacrificed after 7 day. Morphometric analysis of the AN degeneration was immunhistologically determined by spiral ganglion neuron (SGN) serial counts. Confirmation of the deafening process in 7day group was done by auditory brainstem response.

Results: Following the establishment of the housekeeping gene Rplp2 (ribosomal protein) as the internal standard we found an increase in the RNA level of GDNF and the receptors GFRα1, p75 and trkB demonstrating an early upregulation of neurotrophic factor. A significant 1.8 fold decrease of the SGN was demonstrated following 7 days deafening indicating strong apoptosis process.

Conclusion: In general, gene expression data cannot be related to function, however, they allow the verification of the neurotrophin hypothesis. As well, gene expression profiling may clarify the role of neurotrophic factors in the deafening process within the time intervall of deafness.

Supported by: Georg Christoph Lichtenberg Scholarship, Lower Saxony