Perinatal thiamine deficiency causes cochlear innervation abnormalities in mice

Neonatal thiamine deficiency can cause auditory neuropathy in humans. To probe the underlying cochlear pathology, mice were maintained on a thiamine-free or low-thiamine diet during fetal development or early postnatal life. At postnatal ages from 18 days to 22 wks, cochlear function was tested and cochlear histopathology analyzed by plastic sections and cochlear epithelial whole-mounts immunostained for neuronal and synaptic markers. Although none of the thiamine-deprivation protocols resulted in any loss of hair cells or any obvious abnormalities in the non-sensory structures of the cochlear duct, all the experimental groups showed significant anomalies in the afferent or efferent innervation. Afferent synaptic counts in the inner and outer hair cell areas were reduced, as was the efferent innervation density in both the outer and inner hair cell areas. As expected for primary neural degeneration, the thresholds for distortion product otoacoustic emissions were not affected, and as expected for subtotal hair cell de-afferentation, the suprathreshold amplitudes of auditory brainstem responses were more affected than the response thresholds. We conclude that the auditory neuropathy from thiamine deprivation could be produced by loss of inner hair cell synapses.