Reinnervation of hair cells by auditory neurons after selective removal of spiral ganglion neurons.
Hearing loss can be caused by primary degeneration of spiral ganglion neurons or by secondary degeneration of these neurons after hair cell loss. The replacement of auditory neurons would be an important step in any attempt to restore auditory function in patients with damaged inner ear neurons or hair cells. Application of beta-bungarotoxin, a toxin derived from snake venom, to an explant of the cochlea eradicates spiral ganglion neurons while sparing the other cochlear cell types. The toxin was found to bind to the neurons and to cause apoptotic cell death without affecting hair cells or other inner ear cell types as indicated by TUNEL staining, and, thus, the toxin provides a highly specific means of deafferentation of hair cells. We therefore used the denervated organ of Corti for the study of neuronal regeneration and synaptogenesis with hair cells and found that spiral ganglion neurons obtained from the cochlea of an untreated newborn mouse reinnervated hair cells in the toxin-treated organ of Corti and expressed synaptic vesicle markers at points of contact with hair cells. These findings suggest that it may be possible to replace degenerated neurons by grafting new cells into the organ of Corti.
Martinez-Monedero
Rodrigo
R
Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Corrales
C Eduardo
CE
Cuajungco
Math P
MP
Heller
Stefan
S
Edge
Albert S B
AS
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002038:Bungarotoxins; D003056:Cochlear Nerve / Q000166:cytology / Q000502:physiology*; D018920:Coculture Techniques; D003714:Denervation; D004195:Disease Models, Animal; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D006198:Hair Cells, Auditory / Q000166:cytology / Q000502:physiology*; D006319:Hearing Loss, Sensorineural / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000139:chemically induced / Q000503:physiopathology; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009498:Neurotoxins; D013136:Spiral Ganglion / Q000166:cytology / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure
D015415:Biomarkers; D002038:Bungarotoxins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins