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.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Jin D,Ohlemiller KK,Lei D,Dong E,Role L,Ryugo DK,Bao Jdoi
10.1016/j.neurobiolaging.2010.05.011subject
Has Abstractpub_date
2011-12-01 00:00:00pages
2321.e13-23issue
12eissn
0197-4580issn
1558-1497pii
S0197-4580(10)00225-3journal_volume
32pub_type
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journal_title：Neurobiology of aging
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