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

Environmental Health and Preventive Medicine, Dec 2017

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.

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

Gai et al. Environmental Health and Preventive Medicine Effects of chronic noise on the corticotropin-releasing factor system in the rat hippocampus: relevance to Alzheimer's disease-like tau hyperphosphorylation Zhihui Gai 0 1 2 3 Donghong Su 0 1 2 3 Yawen Wang 1 2 Wenlong Li 2 5 Bo Cui 2 4 Kang Li 2 Xiaojun She 2 Rui Wang 0 0 Shandong Academy of Occupational Health and Occupational Medicine , 18877, Jingshi Road, Lixia District, Jinan 250062 , China 1 Equal contributors 2 Department of Occupational Hygiene, Tianjin Institute of Health and Environmental Medicine , Tianjin 300050 , China 3 Shengli Oil Field Central Hospital , Dongying 257034 , China 4 Department of Occupational Hygiene, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences , 1, Dali Road, Heping District, Tianjin 300050 , China 5 School of Public Health and Management, Weifang Medical University , Weifang , China 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. Noise; Hippocampus; Corticotropin-releasing factor receptors; Phosphorylated tau Background There are a great variety of adverse health effects induced by chronic environmental noise, including annoyance, hearing loss, cognitive impairment, cardiovascular disease, and increased risk of diabetes [ 1–3 ]. A number of reports have focused on the AD-like neuropathology, especially hyperphosphorylation of tau protein in the rodent hippocampus, due to the acute or chronic noise exposure [ 4, 5 ]. However, the underlying mechanisms of noise exposure to AD-like tau hyperphosphorylation in the hippocampus, a key structure in cognition and the initial area of tau pathology in AD [6], are still not well understood. The corticotropin-releasing factor (CRF) signaling system plays a well-established role in triggering stress responses and acts as a general mediator/integrator of stress adaptations, whose receptors, CRF receptor 1 (CRFR1) and CRFR2, exert convergent biological effects on stress-related endpoints [ 7 ]. The dysregulation of the CRF signaling system in the hippocampus causes an AD-like pathology in animals [ 8–10 ]. Supporting a role for CRF in AD neuropathology, work from many laboratories has demonstrated that both CRF overexpression and acute or repeated exposure to stressors induce phosphorylation of tau and accumulation of Aβ within the hippocampus, a process that is dependent on CRFR1 [ 11, 12 ]. However, only limited information is available on the control of this system in the hippocampus under chronic noise stress. In this study, we have investigated the effects of longterm noise exposure on the CRF signaling system and explored the relationship between CRF and noiseinduced AD-like changes in the rat hippocampus. Our data could implicate CRF-dependent mechanisms in the neuropathophysiology induced by environmental noise. Methods Animals and experimental groups Male Wistar rats (weighing 200–220 g, Lab Animal Center, Tianjin Institute of Health and Environmental Medicine, Tianjin, China) were used in the present study. All experimental procedures were performed in accordance with the guidelines approved by the Animal and Human Use in Research Committee of the Tianjin Institute of Health and Environmental Medicine. The rats were randomly divided into the noise-exposed group and the control group (32 rats per group). At different time points (days 0, 3, 7, and 14) after the final exposure, all rats i (...truncated)


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Zhihui Gai, Donghong Su, Yawen Wang, Wenlong Li, Bo Cui, Kang Li, Xiaojun She, Rui Wang. Effects of chronic noise on the corticotropin-releasing factor system in the rat hippocampus: relevance to Alzheimer’s disease-like tau hyperphosphorylation, Environmental Health and Preventive Medicine, 2017, pp. 79, Volume 22, Issue 1, DOI: 10.1186/s12199-017-0686-8