Requirement of nicotinic acetylcholine receptor subunit beta2 in the maintenance of spiral ganglion neurons during aging

Age-related hearing loss (presbycusis) is a major health concern for the elderly. Loss of spiral ganglion neurons (SGNs), the primary sensory relay of the auditory system, is associated consistently with presbycusis. The causative molecular events responsible for age-related loss of SGNs are unknown...

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Bibliographic Details
Published in:The Journal of neuroscience 2005-03, Vol.25 (12), p.3041
Main Authors: Bao, Jianxin, Lei, Debin, Du, Yafei, Ohlemiller, Kevin K, Beaudet, Arthur L, Role, Lorna W
Format: Article
Language:English
Subjects:
Acoustic Stimulation - methods
Age Factors
Aging - metabolism
Animals
Blotting, Northern - methods
Blotting, Western - methods
Cadherins - genetics
Disease Models, Animal
Dose-Response Relationship, Radiation
Evoked Potentials, Auditory, Brain Stem - genetics
Gene Expression Regulation - physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Mutant Strains
Neurons - metabolism
Presbycusis - genetics
Presbycusis - metabolism
Presbycusis - physiopathology
Protein Subunits - deficiency
Protein Subunits - genetics
Protein Subunits - metabolism
Receptors, Nicotinic - deficiency
Receptors, Nicotinic - genetics
Receptors, Nicotinic - metabolism
Receptors, Nicotinic - physiology
Reverse Transcriptase Polymerase Chain Reaction - methods
RNA, Messenger - metabolism
Spiral Ganglion - cytology
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Summary:Age-related hearing loss (presbycusis) is a major health concern for the elderly. Loss of spiral ganglion neurons (SGNs), the primary sensory relay of the auditory system, is associated consistently with presbycusis. The causative molecular events responsible for age-related loss of SGNs are unknown. Recent reports directly link age-related neuronal loss in cerebral cortex with the loss of high-affinity nicotine acetylcholine receptors (nAChRs). In cochlea, cholinergic synapses are made by olivocochlear efferent fibers on the outer hair cells that express alpha9 nAChR subunits and on the peripheral projections of SGNs that express alpha2, alpha4-7, and beta2-3 nAChR subunits. A significantly decreased expression of the beta2 nAChR subunit in SGNs was found specifically in mice susceptible to presbycusis. Furthermore, mice lacking the beta2 nAChR subunit (beta2-/-), but not mice lacking the alpha5 nAChR subunit (alpha5-/-), have dramatic hearing loss and significant reduction in the number of SGNs. Our findings clearly established a requirement for beta2 nAChR subunit in the maintenance of SGNs during aging.
ISSN:1529-2401
1529-2401
DOI:10.1523/JNEUROSCI.5277-04.2005