Abstract
Inner ear innervation is regulated by growth factors including neurotrophins. Neurotrophins include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5). Each of the neurotro-phins selectively binds to the high affinity receptors designated as TrkA for NGF, TrkB for BDNF and NT-4/5, and TrkC for NT-3, whereas all neurotrophins bind to the low affinity receptor designated as p75. BDNF and NT-3, but not NGF or NT4/5, are expressed in most sensory epithelia of the inner ear. TrkB and TrkC, but not TrkA, are expressed in cochlear and vestibular ganglia. Analyses of mice lacking BDNF revealed a marked reduction of afferent innervation by vestibular ganglion cells. By contrast, a marked loss of cochlear ganglion cells occured in mice lacking NT-3. No deficits in cochlear or vestibular structures occur in mice lacking either NGF or NT-4/5. Moreover, nearly complete loss of both vestibular and cochlear ganglion cells is shown in double mutant mice lacking both BDNF and NT-3. These observations indicate that BDNF and NT-3 play crucial roles in the development and maintenance of afferent innervation of the inner ear. Local application of neurotrophins may be useful for the treatment of hearing loss.
