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Title

Delayed inner ear maturation and neuronal loss in postnatal Igf-1-deficient mice

AuthorsCamarero, Guadalupe ; Avendaño, Carlos; Fernández-Moreno, Carmen; Villar, Ángeles; Contreras, Julio ; Pablo, Flora de ; Pichel, José G. ; Varela-Nieto, Isabel
KeywordsCochlear ganglion
Insulin-like growth factor 1
IGF-1
Myelination
Neurogenesis
Organ of Corti
Synaptogenesis
Stereology
Issue Date1-Oct-2001
PublisherSociety for Neuroscience
CitationJournal of Neuroscience 21(19): 7630-7641 (2001)
AbstractInsulin-like growth factor-1 (IGF-1) has been shown to play a key role during embryonic and postnatal development of the CNS, but its effect on a sensory organ has not been studied in vivo. Therefore, we examined cochlear growth, differentiation, and maturation in Igf-1 gene knock-out mice at postnatal days 5 (P5), P8, and P20 by using stereological methods and immunohistochemistry. Mutant mice showed reduction in size of the cochlea and cochlear ganglion. An immature tectorial membrane and a significant decrease in the number and size of auditory neurons were also evident at P20. IGF-1-deficient cochlear neurons showed increased caspase-3-mediated apoptosis, along with aberrant expression of the early neural markers nestin and Islet 1/2. Cochlear ganglion and fibers innervating the sensory cells of the organ of Corti presented decreased levels of neurofilament and myelin P(0) in P20 mouse mutants. In addition, an abnormal synaptophysin expression in the somata of cochlear ganglion neurons and sensory hair cells suggested the persistence of an immature pattern of synapses distribution in the organ of Corti of these animals. These results demonstrate that lack of IGF-1 in mice severely affects postnatal survival, differentiation, and maturation of the cochlear ganglion cells and causes abnormal innervation of the sensory cells in the organ of Corti.
Description12 pages, 7 figures, 2 tables.
Publisher version (URL)http://www.jneurosci.org/cgi/content/full/21/19/7630
URIhttp://hdl.handle.net/10261/24335
ISSN0270-6474
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