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.

Dr. rer. nat Jennifer Schulze

Klinik für Hals-, Nasen-, Ohrenheilkunde, Medizinische Hochschule,

Carl-Neuberg-Str. 1, 30625

Hannover

Email: [e-mail]

Publication History

Publication Date:
23 April 2019 (online)