An antibody to RGMa promotes regeneration of cochlear synapses after noise exposure.

Auditory neuropathy is caused by the loss of afferent input to the brainstem via the components of the neural pathway comprising inner hair cells and the first order neurons of the spiral ganglion. Recent work has identified the synapse between cochlear primary afferent neurons and sensory hair cells as a particularly vulnerable component of this pathway. Loss of these synapses due to noise exposure or aging results in the pathology identified as hidden hearing loss, an initial stage of cochlear dysfunction that goes undetected in standard hearing tests.

Trk agonist drugs rescue noise-induced hidden hearing loss.

TrkB agonist drugs are shown here to have a significant effect on the regeneration of afferent cochlear synapses after noise-induced synaptopathy. The effects were consistent with regeneration of cochlear synapses that we observed in vitro after synaptic loss due to kainic acid-induced glutamate toxicity and were elicited by administration of TrkB agonists, amitriptyline, and 7,8-dihydroxyflavone, directly into the cochlea via the posterior semicircular canal 48 hours after exposure to noise. Synaptic counts at the inner hair cell and wave 1 amplitudes in the auditory brainstem response (ABR) were partially restored 2 weeks after drug treatment.

Hair Cell Loss Induced by Sphingosine and a Sphingosine Kinase Inhibitor in the Rat Cochlea.

Sphingolipid metabolites including ceramide, sphingosine (Sph), and sphingosine-1-phosphate (S1P) play important roles in the regulation of cell survival and death. Sphingosine kinase (Sk) phosphorylates Sph to S1P. Sk is reportedly overexpressed in various cancer cells, and Sk inhibitors are therefore a target of anti-tumor therapy.