Institute for Biology and Molecular Genetics
Thomas Schimmang

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Neurotrophin signaling

The roles of neurotrophins and their receptors for innervation of the inner ear

Our studies have revealed which of the neurotrophins and their receptors, termed Trks are essential for the innervation of the inner ear in avians and mammals. Using viral gene transfer and the study of mouse mutants we could conclude that the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) acting via their high-affinity receptors TrkB and TrkC control the survival and differentiation of auditory and vestibular sensory neurons. We have now focussed on several animal models which mimic hearing impairment which may occur during ageing in humans. A significant reduction of BDNF transcripts in high-frequency processing cochlear neurons was observed during aging, though this did not coincide with a major reduction of BDNF protein. In contrast, BDNF protein in peripheral and central projections was drastically reduced. Our results suggest that reduced BDNF protein levels in auditory nerves over age may be a crucial factor in the altered brainstem plasticity observed during presbycusis. Recently we have created conditional mouse mutants lacking BDNF in the auditory system. Interestingly, these mutants appear to be protected against noise damage.

Recent publications:

*L. Rüttiger, *R. Panford-Walsh *T. Schimmang, J. Tan, U. Zimmermann, K. Rohbock, I. Köpschall, A. Limberger, M. Müller, J.–T. Fraenzer, J. Cimerman, and M. Knipper. (2007). BDNF mRNA expression and protein localization are changed in age-related hearing loss.
*Equal contribution 
Neurobiol. of Aging 28, 586-601.

A. Zuccotti, S. Kuhn, S.L. Johnson, C. Franz, W. Singer, D. Hecker, H.-S. Geisler, I. Köpschall, K. Rohbock, K. Gutsche, J. Dlugaiczyk, B. Schick, W. Marcotti, L. Rüttiger, T. Schimmang and M. Knipper. Brain-derived neurotrophic factor both protects and damages inner hair cell synapse physiology.



Instituto de Biología y Genética Molecular
Universidad de Valladolid - Consejo Superior de Investigaciones CIentíficas
C/ Sanz y Forés s/n
47003 - Valladolid - SPAIN
Phone: (+34) 983-184-818 Fax: (+34) 983-184-800

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