NT-3 and/or BDNF therapy prevents loss of auditory neurons following loss of hair cells.
Destruction of auditory hair cells results in a subsequent loss of auditory neurons. In situ hybridization and neuronal cell culture studies as well as analyses of the inner ears of neurotrophin and neurotrophin receptor gene knockout mice have shown that NT-3 and BDNF mediate both the development and survival of auditory neurons. In this study guinea pigs were exposed to the ototoxic combination of an aminoglycoside antibiotic and a loop diuretic and then received 8 weeks of intracochlear infusion of either NT-3, BDNF or NT-3 + BDNF to determine whether site-specific application of these neurotrophins could prevent the loss of auditory neurons that follows a loss of auditory hair cells. Infusion of either NT-3 or NT-3 + BDNF into the scala tympani resulted in a > 90% survival of auditory neurons while BDNF infusion yielded a 78% survival rate, compared with a 14-24% neuronal survival rate in untreated ototoxin-exposed cochleae. These results show that loss of auditory neurons that occurs subsequent to a loss of auditory hair cells can be prevented by in vivo neurotrophin therapy with either NT-3 or BDNF.
Staecker
H
H
Department of Otolaryngology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Kopke
R
R
Malgrange
B
B
Lefebvre
P
P
Van de Water
T R
TR
D000818:Animals; D001306:Auditory Pathways / Q000166:cytology / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use*; D002452:Cell Count / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003051:Cochlea / Q000166:cytology / Q000187:drug effects; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects*; D020933:Neurotrophin 3; D013136:Spiral Ganglion / Q000166:cytology / Q000187:drug effects
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3