Mechanisms Underlying Noise-Induced PV+ Neuron Loss

Abstract

There is a decrease of PV+ neurons in the primary auditory cortex of noise-exposed C57BL/6 mice. However, the mechanism behind this decrease was not clear. Therefore, the primary purpose of this study was to assess the possible cell death mechanisms involved in PV+ reduction. To help us identify potential cell death mechanisms to further look into, we first compared PV+ neuron reduction in noise-exposed C57BL/6 mice to noise-exposed FVB mice. C57BL/6 and FVB strains have different immune response profiles. Therefore, differences in PV+ neuron reduction in the primary auditory cortex of these two mouse strains can imply that pro-inflammatory cytokines might have a role in PV+ neuron density reduction. We observed different gap detection patterns and differences in PV+ neuron loss in the primary auditory cortex between noise-exposed C57BL/6 and FVB mice. Noise-exposed C57BL/6 mice displayed impairments in gap detection and reduction in PV+ neuron density in the primary auditory cortex. However, noise-exposed FVB mice did not show impairments in gap detection, and there was no change in their PV+ neuron density. Based on this finding, as well as previous studies linking tinnitus to pro-inflammatory cytokines, we examined PV+ neurons of noise-exposed C57BL/6 mice for signs of apoptosis and necroptosis. Both of these cell death mechanisms can be triggered by pro-inflammatory cytokines. TUNEL staining was used to identify apoptosis. Immunohistochemistry staining with the RIP3 primary antibody was used as a marker for necroptosis. We did not observe apoptosis in PV+ neurons in the primary auditory cortex of noise-exposed mice. Necroptosis was observed in PV+ neurons in the primary auditory cortex of noise-exposed mice (p < 0.05). Therefore, necroptosis might play a role in the observed PV+ loss in the primary auditory cortex of noise-exposed mice.