Age-related neuronal loss in the cochlea is not delayed by synaptic modulation

Abstract Age-related synaptic change is associated with the functional decline of the nervous system. It is unknown whether this synaptic change is the cause or the consequence of neuronal cell loss. We have addressed this question by examining mice genetically engineered to over- or underexpress ne...

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Bibliographic Details
Published in:Neurobiology of aging 2011-12, Vol.32 (12), p.2321.e13-2321.e23
Main Authors: Jin, David, Ohlemiller, Kevin K, Lei, Debin, Dong, Elizabeth, Role, Lorna, Ryugo, David K, Bao, Jianxin
Format: Article
Language:English
Subjects:
Acoustic Stimulation - methods
Aging
Aging - metabolism
Aging - pathology
Animals
Cell Count - methods
Cell Survival - physiology
Cochlea
Cochlea - innervation
Cochlea - metabolism
Cochlea - pathology
Hearing Loss - metabolism
Hearing Loss - pathology
Internal Medicine
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neuregulin-1
Neuregulin-1 - genetics
Neuregulin-1 - physiology
Neurology
Presbycusis
Spiral Ganglion - pathology
Spiral ganglion neuron
Synapses - pathology
Synapses - physiology
Synaptic Transmission - physiology
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Summary:Abstract Age-related synaptic change is associated with the functional decline of the nervous system. It is unknown whether this synaptic change is the cause or the consequence of neuronal cell loss. We have addressed this question by examining mice genetically engineered to over- or underexpress neuregulin-1 ( NRG1 ), a direct modulator of synaptic transmission. Transgenic mice overexpressing NRG1 in spiral ganglion neurons (SGNs) showed improvements in hearing thresholds, whereas NRG1 −/+ mice show a complementary worsening of thresholds. However, no significant change in age-related loss of SGNs in either NRG1 −/+ mice or mice overexpressing NRG1 was observed, while a negative association between NRG1 expression level and survival of inner hair cells during aging was observed. Subsequent studies provided evidence that modulating NRG1 levels changes synaptic transmission between SGNs and hair cells. One of the most dramatic examples of this was the reversal of lower hearing thresholds by “turning-off” NRG1 overexpression. These data demonstrate for the first time that synaptic modulation is unable to prevent age-related neuronal loss in the cochlea.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2010.05.011