Expression pattern of brain-derived neurotrophic factor and its associated receptors: Implications for exogenous neurotrophin application

• Published in: Hearing research Vol. 413; p. 108098
• Main Authors: Schulze, Jennifer, Staecker, Hinrich, Wedekind, Dirk, Lenarz, Thomas, Warnecke, Athanasia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2022
• Subjects: Animals; Brain-Derived Neurotrophic Factor; Mature BDNF; Mice; Neurotrophins; NTRK2; Organ of Corti; P75NTR; ProBDNF; Receptors, Nerve Growth Factor - genetics; Receptors, Nerve Growth Factor - metabolism; Rosenthal's canal; Spiral ganglion neurons; ProBDNF; NTRK2; Rosenthal's canal; Organ of Corti; Mature BDNF; Spiral ganglion neurons; P75NTR; Neurotrophins
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/j.heares.2020.108098

•mBDNF is expressed in the IHC and OHC of the organ of Corti and in the spiral ganglion of the Rosenthal's canal.•proBDNF is expressed in the supporting cells below the OHC.•Both corresponding receptors, NTRK2 and p75NTR, are expressed in the spiral ganglion.•proBDNF is not toxic for dissociated rat spiral ganglion neurons.•proBDNF did not influence the pro-survival and neurite-inducing effects of mBDNF. The application of neurotrophins such as brain-derived neurotrophic factor (BDNF) is a promising pharmacological approach in cochlear implant research. Several in vitro and in vivo studies demonstrated that treatment with neurotrophins support the spiral ganglion neuron (SGN) survival and the synapses. Of the more than 40 companies that are working in the field of inner ear therapeutics, only one company is currently advancing BDNF towards clinical translation. Thus, there are no approved clinical therapies with neurotrophins, their precursors or neurotrophin-like substances. For a better understanding of the mechanisms of BDNF in the inner ear, we analysed the expression of mature BDNF (mBDNF), its pro-form proBDNF and their respective receptors the low affinity p75 neurotrophin receptor (p75NTR) and the neurotrophic receptor tyrosine kinase 2 (NTRK2). In the adult murine inner ear, mBDNF is expressed in the inner and outer hair cells (IHC and OHC) of the organ of Corti and in the spiral ganglion of the Rosenthal's canal, whereas proBDNF is only detected in the supporting cells below the OHC. The corresponding receptors NTRK2 and p75NTR are expressed in the spiral ganglion whereof p75NTR is stronger expressed. For more insights in the effects of mBDNF and proBDNF on inner ear specific cells, we treated primary dissociated SGN with different concentrations of mBDNF and proBDNF alone and in combination. Interestingly, treatment with proBDNF is not toxic for SGN but simultaneously not protective. However, combined treatment of mBDNF and proBDNF maintained and perhaps slightly increased the protective effect of mBDNF. Thus, the mixture of mBDNF and proBDNF could be the new direction for the development of BDNF-based therapeutics in cochlear implantation and could represent more precisely the natural environment.