Trophic effects of insulin-like growth factor-I (IGF-I) in the inner ear.
Insulin-like growth factors (IGFs) have a pivotal role during nervous system development and in its functional maintenance. IGF-I and its high affinity receptor (IGF1R) are expressed in the developing inner ear and in the postnatal cochlear and vestibular ganglia. We recently showed that trophic support by IGF-I is essential for the early neurogenesis of the chick cochleovestibular ganglion (CVG). In the chicken embryo otic vesicle, IGF-I regulates developmental death dynamics by regulating the activity and/or levels of key intracellular molecules, including lipid and protein kinases such as ceramide kinase, Akt and Jun N-terminal kinase (JNK). Mice lacking IGF-I lose many auditory neurons and present increased auditory thresholds at early postnatal ages. Neuronal loss associated to IGF-I deficiency is caused by apoptosis of the auditory neurons, which presented abnormally increased levels of activated caspase-3. It is worth noting that in man, homozygous deletion of the IGF-1 gene causes sensory-neural deafness. IGF-I is thus necessary for normal development and maintenance of the inner ear. The trophic actions of IGF-I in the inner ear suggest that this factor may have therapeutic potential for the treatment of hearing loss.
Instituto de Investigaciones Biomedicas Alberto Sols, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, "Alberto Sols", Arturo Duperier 4, 28029 Madrid, Spain. ivarela@iib.uam.es
Isabel
I
Varela-Nieto
Jose A
JA
Morales-Garcia
Patricia
P
Vigil
Amelia
A
Diaz-Casares
Itziar
I
Gorospe
Susana
S
Sánchez-Galiano
Susana
S
Cañon
Guadalupe
G
Camarero
Julio
J
Contreras
Rafael
R
Cediel
Yolanda
Y
Leon
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D016922:Cellular Senescence / Q000502:physiology; D003051:Cochlea / Q000166:cytology / Q000254:growth & development; D007758:Ear, Inner / Q000196:embryology*; D047108:Embryonic Development / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology*
D007334:Insulin-Like Growth Factor I