Effects of chronic noise on the corticotropin-releasing factor system in the rat hippocampus: relevance to Alzheimer's disease-like tau hyperphosphorylation

Background: Chronic noise exposure has been associated with tau hyperphosphorylation and Alzheimer's disease (AD)-like pathological changes, but the underlying mechanism is unknown. In this study, we explored the effects of long-term noise exposure on the corticotropin-releasing factor (CRF) system in the hippocampus and its role in noise-induced tau phosphorylation. Methods: Sixty-four rats were randomly divided into the noise-exposed group and the control group, and rats in the exposure group were exposed to 95 dB SPL white noise for 30 consecutive days. The levels of CRF, CRFR1, CRFR2, and total tau and phosphorylated tau (p-tau) at Ser396 (S396) and Thr205 (T205) in the hippocampus were measured at different time points after the final noise exposure. The co-localized distribution of CRF and p-tau (T205) in the hippocampus was evaluated using double-labeling immunofluorescence. Results: Long-term exposure to noise for 30 consecutive days significantly increased the expression of CRF and CRFR1 and their mRNAs levels in the hippocampus, which persisted for 7 days after final exposure. In contrast, CRFR2 was raised for 3-7 days following the last exposure. These alterations were also concomitant with the phosphorylation of tau at S396 and T205. Furthermore, there was co-localization of p-tau and CRF in hippocampal neurons. Conclusion: Chronic noise leads to long-lasting increases in the hippocampal CRF system and the hyperphosphorylation of tau in the hippocampus. Our results also provide evidence for the involvement of the CRF system in noise-induced AD-like neurodegeneration.