Chronic noise exposure causes persistence of tau hyperphosphorylation and formation of NFT tau in the rat hippocampus and prefrontal cortex.
2012
Abstract The non-auditory effects of noise exposure on the central nervous system have been established both epidemiologically and experimentally. Chronic noise exposure (CNE) has been associated with tau hyperphosphorylation and Alzheimer's disease (AD)-like pathological changes. However, experimental evidence for these associations remains limited. The aim of the current study was to explore the effects of CNE [100 dB sound pressure level (SPL) white noise, 4 h/d × 14 d] on tau phosphorylation in the rat hippocampus and the prefrontal cortex. Forty-eight male Wistar rats were randomly assigned to two groups: a noise-exposed group and a control group. The levels of radioimmunoprecipitation assay (RIPA)-soluble and RIPA-insoluble phosphorylated tau at Ser202, Ser396, Ser404, and Ser422 in the hippocampus and the prefrontal cortex were measured at different time points (days 0, 3, 7, and 14) after the end of the last noise exposure. Exposure to white noise for 14 consecutive days significantly increased the levels of tau phosphorylation at Ser202, Ser396, Ser404, and Ser422, the sites typically phosphorylated in AD brains, in the hippocampus and the prefrontal cortex. Tau hyperphosphorylation persisted for 7 to 14 d after the cessation of noise exposure. These alterations were also concomitant with the generation of pathological neurofibrillary tangle (NFT) tau 3, 7 and 14 d after the end of the stimulus. Furthermore, lasting increases in proteins involved in hyperphosphorylation, namely glycogen synthase kinase 3β (GSK3β) and protein phosphatase 2A (PP2A), were found to occur in close correspondence with increase in tau hyperphosphorylation. The results of this study show that CNE leads to long-lasting increases in non-NFT hyperphosphorylated tau and delayed formation of misfolded NFT tau in the hippocampus and the prefrontal cortex. Our results also provide evidence for the involvement of GSK3β and PP2A in these processes.
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