Glial cell line-derived neurotrophic factor (GDNF) and its receptor complex are expressed in the auditory nerve of the mature rat cochlea

Glial cell line-derived neurotrophic factor (GDNF) is a survival factor for many neuronal cell types which signals through a heterodimer receptor consisting of GDNF-family receptor alpha 1 (GFR alpha -1) and Ret (rearranged during transformation). GDNF expression has previously been reported in the inner hair cells of the rat cochlea, with expression of GFR alpha -1 but not Ret in the cell bodies of the auditory nerve (spiral ganglion cells), using in situ hybridization. The present study used reverse transcription-polymerase chain reaction (RT-PCR), and immunocytochemistry to examine GDNF, GFR alpha -1 and Ret in the adult rat auditory nerve. Semi-quantitative RT-PCR showed expression of GDNF and the two receptor components, GFR alpha -1 and Ret, in the modiolar subfraction of the cochlea containing spiral ganglion cells. A shorter mRNA splice variant for GDNF was also detected. Immunocytochemistry showed immunostaining in the modiolus for GDNF, GFR alpha -1 and Ret that was confined to spiral ganglion cells. When RT-PCR expression levels were compared to the expression in the substantia nigra, GFR alpha -1 expression levels were similar, Ret mRNA was lower in the modiolus and GDNF expression was higher in the modiolus. However, when GDNF was further assessed using Western blot, while GDNF protein was found in the modiolus it was at lowe cr levels than in substantia nigra tissue. These results demonstrate that GDNF and both of its receptor components are found in spiral ganglion cells of the adult rat cochlea. Along with the previous report of GDNF in inner hair cells, these new results provide a basis for the role of GDNF as a survival factor for the auditory nerve, as suggested by previous studies. (C) 2001 Published by Elsevier Science B.V.