Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Weihua Wang
  • Li S. Zhang
  • Alexander K. Zinsmaier
  • Genevieve Patterson
  • Emily Jean Leptich
  • Savannah L. Shoemaker
  • Tatiana A. Yatskievych
  • Robert Gibboni
  • Edward Pace
  • Hao Luo
  • Jinsheng Zhang
  • Shaowen Bao

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Detail(s)

Original languageEnglish
Article numbere3000307
Journal / PublicationPLoS Biology
Volume17
Issue number6
Online published18 Jun 2019
Publication statusPublished - Jun 2019

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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-α) or pharmacologically blocking TNF-α expression prevented neuroinflammation and ameliorated the behavioral phenotype associated with tinnitus in mice with NIHL. Conversely, infusion of TNF-α into AI resulted in behavioral signs of tinnitus in both wild-type and TNF-α 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-α expression. These results implicate neuroinflammation as a therapeutic target for treating tinnitus and other hearing loss-related disorders.

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Citation Format(s)

Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models. / Wang, Weihua; Zhang, 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.

In: PLoS Biology, Vol. 17, No. 6, e3000307, 06.2019.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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