Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models
Zhang, Li S
Zinsmaier, Alexander K
Leptich, Emily Jean
Shoemaker, Savannah L
Yatskievych, Tatiana A
AffiliationUniv Arizona, Dept Physiol
MetadataShow full item record
PublisherPUBLIC LIBRARY SCIENCE
CitationWang, 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.
Rights© 2019 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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AbstractHearing 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.
NoteOpen access journal
VersionFinal published version
SponsorsNational 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 
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- Authors: Takacs JD, Forrest TJ, Basura GJ
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- Authors: Tan J, Rüttiger L, Panford-Walsh R, Singer W, Schulze H, Kilian SB, Hadjab S, Zimmermann U, Köpschall I, Rohbock K, Knipper M
- Issue date: 2007 Mar 16