Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models
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journal.pbio.3000307.pdf
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Author
Wang, WeihuaZhang, Li S
Zinsmaier, Alexander K
Patterson, Genevieve
Leptich, Emily Jean
Shoemaker, Savannah L
Yatskievych, Tatiana A
Gibboni, Robert
Pace, Edward
Luo, Hao
Zhang, Jinsheng
Yang, Sungchil
Bao, Shaowen
Affiliation
Univ Arizona, Dept PhysiolIssue Date
2019-06
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PUBLIC LIBRARY SCIENCECitation
Wang, W., Zhang, L. S., Zinsmaier, A. K., Patterson, G., Leptich, E. J., Shoemaker, S. L., ... & Zhang, J. (2019). Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models. PLoS biology, 17(6), e3000307.Journal
PLOS BIOLOGYRights
© 2019 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Hearing loss is a major risk factor for tinnitus, hyperacusis, and central auditory processing disorder. Although recent studies indicate that hearing loss causes neuroinflammation in the auditory pathway, the mechanisms underlying hearing loss-related pathologies are still poorly understood. We examined neuroinflammation in the auditory cortex following noise-induced hearing loss (NIHL) and its role in tinnitus in rodent models. Our results indicate that NIHL is associated with elevated expression of proinflammatory cytokines and microglial activation-two defining features of neuroinflammatory responses-in the primary auditory cortex (AI). Genetic knockout of tumor necrosis factor alpha (TNF-alpha) or pharmacologically blocking TNF-alpha expression prevented neuroinflammation and ameliorated the behavioral phenotype associated with tinnitus in mice with NIHL. Conversely, infusion of TNF-alpha into AI resulted in behavioral signs of tinnitus in both wild-type and TNF-alpha knockout mice with normal hearing. Pharmacological depletion of microglia also prevented tinnitus in mice with NIHL. At the synaptic level, the frequency of miniature excitatory synaptic currents (mEPSCs) increased and that of miniature inhibitory synaptic currents (mIPSCs) decreased in AI pyramidal neurons in animals with NIHL. This excitatory-to-inhibitory synaptic imbalance was completely prevented by pharmacological blockade of TNF-alpha expression. These results implicate neuroinflammation as a therapeutic target for treating tinnitus and other hearing loss-related disorders.Note
Open access journalISSN
1544-9173EISSN
1545-7885PubMed ID
31211773Version
Final published versionSponsors
National Institute of Health [DC009259, DC014335]; Department of Defense [W81XWH-15-1-0028, W81XWH-15-1-0356, W81XWH-15-1-0357]; Food and Health Bureau of Hong Kong Special Administrative Region Government [04150076]ae974a485f413a2113503eed53cd6c53
10.1371/journal.pbio.3000307
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Except where otherwise noted, this item's license is described as © 2019 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.