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DOI: 10.1055/s-0039-1686503
The two froms of neurotrophins and their neuroprotective effect on inner ear specific cells
Introduction:
Numerous in vitro and in vivo studies show that neurotrophins protect the cells of the inner ear from degeneration. Therefore, the administration of neurotrophins is a promising pharmacological approach in cochlear implant research. Neurotrophins, however, are highly increased and released endogenously, initially as a pro-form, which is then converted into the mature form by proteolytic cleavage. Generally, brain-derived neurotrophic factor (BDNF) is administered in its mature form. The aim of this study is to investigate whether pro-BDNF, despite its apoptosis-inducing properties, can be administered to maintain endogenous homeostasis between pro-BDNF and BDNF.
Material:
First, the expression of both BDNF forms and their receptors in the murine cochlea was analyzed by immunocytochemical antibody staining. Additionally, dissociated spiral ganglion cells (SGC) from neonatal rats (P3 – 5) were incubated with BDNF and pro-BDNF alone as well as in combination and the survival rates were determined.
Results:
Both forms and their corresponding receptors are expressed in the organ of Corti and in the spiral ganglion of adult cochleae. Treatment with pro-BDNF alone has no neuroprotective effect but also no toxic effect on SGC. When administered in combination with BDNF, pro-BDNF increases the survival rate of SGC (both forms are almost in equilibrium) and reduces the survival rate (imbalance between the two forms).
Conclusion:
These results suggest that a balanced ratio of pro-BDNF and mature BDNF matches more precisely the physiological conditions in the cochlea and may even mediate the neuroprotective effect.
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Publication History
Publication Date:
23 April 2019 (online)
© 2019. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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