Inactivation of fibroblast growth factor receptor signaling in myelinating glial cells results in significant loss of adult spiral ganglion neurons accompanied by age-related hearing impairment.
J Neurosci Res
; 87(15): 3428-37, 2009 Nov 15.
Article
de En
| MEDLINE
| ID: mdl-19598249
ABSTRACT
Hearing loss has been attributed to many factors, including degeneration of sensory neurons in the auditory pathway and demyelination along the cochlear nerve. Fibroblast growth factors (FGFs), which signal through four receptors (Fgfrs), are produced by auditory neurons and play a key role in embryonic development of the cochlea and in neuroprotection against sound-induced injury. However, the role of FGF signaling in the maintenance of normal auditory function in adult and aging mice remains to be elucidated. Furthermore, the contribution of glial cells, which myelinate the cochlear nerves, is poorly understood. To address these questions, we generated transgenic mice in which Fgfr1 and Fgfr2 were specifically inactivated in Schwann cells and oligodendrocytes but not in neurons. Adult mutant mice exhibited late onset of hearing impairment, which progressed markedly with age. The hearing impairment was accompanied by significant loss of myelinated spiral ganglion neurons. The pathology extended into the cochlear nucleus, without apparent loss of myelin or of the deletion-bearing glial cells themselves. This suggests that perturbation of FGF receptor-mediated glial function leads to the attenuation of glial support of neurons, leading to their loss and impairment of auditory functions. Thus, FGF/FGF receptor signaling provides a potentially novel mechanism of maintaining reciprocal interactions between neurons and glia in adult and aging animals. Dysfunction of glial cells and FGF receptor signaling may therefore be implicated in neurodegenerative hearing loss associated with normal aging.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Vieillissement
/
Ganglion spiral
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Névroglie
/
Récepteur FGFR1
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Surdité neurosensorielle
/
Dégénérescence nerveuse
Limites:
Animals
Langue:
En
Journal:
J Neurosci Res
Année:
2009
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique