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Front Aging Neurosci. 2015 Jul 24;7:145. doi: 10.3389/fnagi.2015.00145. eCollection 2015.

Dendrogenin A and B two new steroidal alkaloids increasing neural responsiveness in the deafened guinea pig.

Author information

1
Department of Neuroscience, Karolinska Institutet Stockholm, Sweden.
2
Affichem SA Toulouse, France.
3
INSERM UMR 1037, Cancer Research Center of Toulouse Toulouse, France.

Abstract

AIM:

To investigate the therapeutic potential for treating inner ear damage of two new steroidal alkaloid compounds, Dendrogenin A and Dendrogenin B, previously shown to be potent inductors of cell differentiation.

METHODS:

Guinea pigs, unilaterally deafened by neomycin infusion, received a cochlear implant followed by immediate or a 2-week delayed treatment with Dendrogenin A, Dendrogenin B, and, as comparison artificial perilymph and glial cell-line derived neurotrophic factor. After a 4-week treatment period the animals were sacrificed and the cochleae processed for morphological analysis. Electrically-evoked auditory brainstem responses (eABRs) were measured weekly throughout the experiment.

RESULTS:

Following immediate or delayed Dendrogenin treatment the electrical responsiveness was significantly maintained, in a similar extent as has been shown using neurotrophic factors. Histological analysis showed that the spiral ganglion neurons density was only slightly higher than the untreated group.

CONCLUSIONS:

Our results suggest that Dendrogenins constitute a new class of drugs with strong potential to improve cochlear implant efficacy and to treat neuropathy/synaptopathy related hearing loss. That electrical responsiveness was maintained despite a significantly reduced neural population suggests that the efficacy of cochlear implants is more related to the functional state of the spiral ganglion neurons than merely their number.

KEYWORDS:

auditory nerve; cochlear implant; electrically-evoked auditory brainstem response; spiral ganglion neuron; steroidal alkaloid

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