Rho-GTPase and p38 mediated neuroprotection in spiral ganglion cells

Introduction:

The administration of neuroprotective and neuroregenerative factors is of great importance in the field of cochlear implant (CI) research. Particularly with regard to the development of novel biological therapies, the identification of suitable substances is essential. Own preliminary work has shown that Clostridium botulinum C3 (C3_bot) protects spiral ganglion cells (SGC). The aim of this study is the identification of intracellular signaling pathways through which this neuroprotective effect is mediated.

Method:

First, SGC were isolated from neonatal rats and cultured with 50 nM of C3_bot, an enzymatically inactive mutant C3_bot_E174/Q and a C3-derived 26mer peptide C3_bot_156 – 181 alone and in combination with brain-derived neurotrophic factor (BDNF). Subsequently, further tests were performed in combination with 5 selected inhibitors in order to investigate through which pathway the neuroprotective effect is mediated.

Results:

Preliminary results showed that the addition of all three C3_bot variants in combination with BDNF results in a significant increase in the survival rate of the SGC. The achieved neuroprotective effect of C3_bot was almost completely revised by the addition of NSC23766 (inhibitor of Rho-GTPase Rac I) and SB203580 (inhibitor of p38 MAPK).

Conclusion:

The effect of C3_bot on SGC is mediated by the Rho-GTPase and p38. A possible application of C3_bot in combination with a CI appears promising.

Publication History

Publication Date:
18 April 2018 (online)