Dataset Information

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

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

SUBMITTER: Wang W

PROVIDER: S-EPMC6581239 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Wang Weihua W Zhang Li S LS Zinsmaier Alexander K AK Patterson Genevieve G Leptich Emily Jean EJ Shoemaker Savannah L SL Yatskievych Tatiana A TA Gibboni Robert R Pace Edward E Luo Hao H Zhang Jinsheng J Yang Sungchil S Bao Shaowen S Bao Shaowen S

PLoS biology 20190618 6

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 express ...[more]

PMID: 31211773

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Project description:BACKGROUND:The phenomenon of short-term tinnitus suppression by different forms of acoustic stimulation is referred to as residual inhibition (RI). RI can be triggered in the majority of tinnitus cases and was found to be depending on the used intensity, length or types of sounds. Past research already stressed the impact of noise stimulation as well as the superiority of amplitude modulated (AM) pure tones at the individual tinnitus frequency for RI in tonal tinnitus. Recently a novel approach for the determination of noise-like tinnitus characteristics was proposed. OBJECTIVES:The aim of the present study was to investigate whether in participants with noise-like tinnitus RI can be increased by AM noise stimuli according to the individual tinnitus frequency range. METHODS:For this purpose the individual tinnitus characteristics (noise-like and tonal tinnitus) of 29 people affected by tinnitus (mean age = 55.59, 7 females, mean tinnitus duration = 159.97 months) were assessed via customizable noise-band matching. The objective was to generate bandpass filtered stimuli according to the individual tinnitus sound (individualized bandpass filtered [IBP] sounds). Subsequently, various stimuli differing in bandpass filtering and AM were tested with respect to their potential to induce RI. Participants were acoustically stimulated with 7 different types of stimuli for 3 min each and had to rate the loudness of their tinnitus after each stimuli. RESULTS:Results indicate a general efficacy of noise stimuli for the temporary suppression of tinnitus, but no significant differences between AM and unmodulated IBP. Significantly better effects were observed for the subgroup with noise-like tinnitus (n = 14), especially directly after stimulation offset. CONCLUSIONS:The study at hand provides further insights in potential mechanisms behind RI for different types of tinnitus. Beyond that, derived principles may qualify for new or extend current tinnitus sound therapies.

Dataset Information

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

Publications

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

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