Neurotrophins, NMDA receptors, and nitric oxide in development and protection of the auditory system.
Neurotrophic factors are secreted peptides that when interacting with specific classes of membrane receptors activate intracellular signaling cascades that prevents neuronal death during embryonic development. The establishment of gene-targeted null mutant mice for the neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) has led to the discovery that they are crucial trophic factors for the survival of auditory and vestibular neurons during development. BDNF is the major survival factor for vestibular ganglion neurons, while NT-3 only support a small number of these neurons. In the cochlea, auditory type I neurons require NT3 for their survival, whereas type II neurons depend on BDNF. With this information at hand recent progress has been made regarding the prevention of aminoglycoside-induced hearing loss in the adult guinea pig. These results and the mechanisms leading to hair cell damage are discussed in this paper.
Agerman
K
K
Department of Medical Biochemistry, Karolinska Institute, Stockholm, Sweden.
Canlon
B
B
Duan
M
M
Ernfors
P
P
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D003638:Deafness / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D007758:Ear, Inner / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D020933:Neurotrophin 3 / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; D020933:Neurotrophin 3; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide