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)