Diffusible Tumor Necrosis Factor-Alpha (TNF-α) Promotes Noise-Induced Parvalbumin-Positive (PV+) Neuron Loss and Auditory Processing Impairments.

Summary

To test whether raised brain proinflammatory cytokines worsen noise damage, TNF-α was infused into the cerebral ventricle of mice, with or without moderate (86 dB) noise exposure. Only the combination of TNF-α infusion and noise, not either alone, reduced the density of parvalbumin-positive (PV+) inhibitory interneurons in the auditory cortex and impaired gap detection and prepulse inhibition (behavioural readouts of auditory processing and tinnitus). This positions disease-related elevations in brain cytokines as a risk factor for noise-induced auditory processing disorder and tinnitus, and connects neuroinflammation mechanistically to the loss of cortical PV inhibition.

Key findings

• TNF-α infusion combined with noise, but neither alone, reduced cortical parvalbumin-positive (PV+) interneuron density.
• The same combination impaired gap detection and prepulse inhibition, behavioural signatures of auditory processing deficits and tinnitus.
• Directly links neuroinflammation (TNF-α) to loss of the cortical PV inhibition central to the PV Interneuron Dysfunction hypothesis.
• Suggests systemic or brain inflammation is a risk factor that amplifies noise-induced auditory damage.