The role of the neurotrophins in maturation and maintenance of postnatal auditory innervation.
Auditory hair cells produce trophic factors that directly affect maturation and survival of auditory neurons. These factors include two members of the neurotrophin family: brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). Loss of hair cells, as a result of either noise trauma or ototoxic damage, results in the degeneration of auditory neurons. An in vitro model of early postnatal rat organ of Corti/spiral ganglion explants was used to study the effects of deprivation and supplementation of nerve growth factor (NGF), BDNF, and NT-3 on neuronal survival. Immunolocalization of receptors for these neurotrophins correlated with their effectiveness as promoters of neuronal survival. BDNF affected early neuronal survival, whereas NT-3 was the most important survival factor for maturing auditory neurons. NGF was shown to maintain axonal morphology. Our results support the hypothesis that changes in the expression of these neurotrophins and their specific receptors in the maturing cochlea may control the postnatal processes of neuronal apoptosis and maturation of the innervation of both inner and outer hair cells. The results suggest that these growth factors have potential for preventing neuronal degeneration as well as enhancing the repair of damaged neuronal processes in the traumatized auditory system.
Staecker
H
H
Department of Otolaryngology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Galinovic-Schwartz
V
V
Liu
W
W
Lefebvre
P
P
Kopke
R
R
Malgrange
B
B
Moonen
G
G
Van De Water
T R
TR
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D006198:Hair Cells, Auditory / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D009410:Nerve Degeneration; D009414:Nerve Growth Factors; D009841:Oligonucleotides / Q000494:pharmacology; D009925:Organ of Corti / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013136:Spiral Ganglion / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009841:Oligonucleotides