Artikel
Regulation of the gene expression of the NGF- und TGFb-family members in the modiolus of deafened rats
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Veröffentlicht: | 22. September 2005 |
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Gliederung
Text
Hair cell loss following drug- and noise-induced trauma induces apoptosis in spiral ganglion cells (SGC). It has been shown that neurotrophic factors (NTF), especially members of the transforming growth factor b (TGF-b) superfamily, play key roles for the protection of SGC and enhance the functional excitability of the auditory nerve in response to stress. However, their molecular mechanisms and signaling pathways remains to be elucidated. The aim of the present study was to determine gene expression patterns of the glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF) and transforming growth factor beta (TGFb) family members and their corresponding receptors in the modiolus and inferior colliculus of deafened rats. Adult rats were deafened by local inner ear injection of 10% neomycin and sacrificed after 26 days. The gene expression of GDNF, persephin, artemin and neurturin, their receptors GFRa1, GFRa2, GFRa3 and c-ret, brain derived neurotrophic factor (BDNF), the tyrosine kinase receptors trk A, B and C, fibroblast growth factor 1 (FGF1) as well as TGFb1, TGFb2, the receptors TGFbR1 and TGFbR2 was determined by semiquantitative RT-PCR using GAPDH expression as an internal standard. No significant changes in gene expression levels of the NTF were found in IC following deafness. In contrast the GDNF family members artemin (ART), GDNF, GFRa1, GFRa3 and c-ret RNA and the NGF and TGFb family members BDNF, TGFb1 and TGFbR1 expression were signuficantly upregulated in modiolus of deafened rats. Only trk B, the BDNF relating receptor, was downregulated in modiolus following hearing loss. These data suggest endogenous survival effects of ART, BDNF, GDNF and TGFb1 on the auditory nerve following neomycin-induced deafness. In addition, there may be specific co-regulatory mechanisms for gene expression of NTFs associated with different nerve growth families.