Role of astrocytes in the repair of auditory synapses in the cochlear nucleus after noise damage

Abstract

Objective·To investigate the pathological and physiological changes underlying noise-induced cochlear nucleus damage and the regulating function of astrocytes on the damage, using a combination of morphological analysis, and molecular biology techniques.Methods·Forty-eight male C57BL/6J mice were randomly divided into two groups and exposed to 110 dB SPL (sound pressure level) broadband noise for 2 hours. Auditory brainstem response (ABR) tests were performed on the mice on days 1, 7, 14, 30, and 90 after the noise exposure. Immunofluorescence staining of cochlear nuclear tissue was conducted to observe cochlear nuclear neurons and auditory synapses, as well as astrocyte activation levels. In addition, the damage to the cochlear nuclear neurons and synapses caused by noise was verified through Western blotting.Results·A significant decrease in cochlear nuclear Bushy cells after noise exposure was observed. The Western blotting results showed that there was severe loss of nerve fibers in cochlear nuclear neurons, indicating that noise caused significant damage to cochlear nucleus neurons. Moreover, a significant loss of auditory synapses labeled with vesicular glutamate transporter 1 (Vglut1) was observed, which was the severest on day 14 after noise exposure and slowly recovered on day 90. Interestingly, astrocytes in the cochlear nucleus displayed obvious clustering and activation after noise exposure. By staining with glial fibrillary acidic protein (GFAP), most astrocytes were distributed around the cochlear nucleus, granule cell area, and auditory nerve root before noise exposure, and they had a small size. However, on day 14 after noise exposure, a large number of activated astrocytes aggregated in the ventral cochlear nucleus, and they all showed a pattern of growth around the synapses.Conclusion·Noise exposure leads to significant damage in the cochlear nucleus, and it is possible that astrocytes are involved in its damage and repair processes. These findings will provide a crucial foundation for further understanding the mechanisms of sound signal analysis, integration, and neural plasticity in the cochlear nucleus.

Keywords

• noise-induced hearing loss
• cochlear nucleus
• astrocytes
• synaptic plasticity