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.
Varela-Nieto
Isabel
I
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
Morales-Garcia
Jose A
JA
Vigil
Patricia
P
Diaz-Casares
Amelia
A
Gorospe
Itziar
I
Sánchez-Galiano
Susana
S
Cañon
Susana
S
Camarero
Guadalupe
G
Contreras
Julio
J
Cediel
Rafael
R
Leon
Yolanda
Y
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