Around-the-Clock Noise Induces AD-like Neuropathology by Disrupting Autophagy Flux Homeostasis

Cells. 2022 Sep 2;11(17):2742. doi: 10.3390/cells11172742.

Abstract

Environmental noise is a common hazard in military operations. Military service members during long operations are often exposed to around-the-clock noise and suffer massive emotional and cognitive dysfunction related to an Alzheimer's disease (AD)-like neuropathology. It is essential to clarify the mechanisms underlying the effects of around-the-clock noise exposure on the central nervous system. Here, Wistar rats were continuously exposed to white noise (95 dB during the on-duty phase [8:00-16:00] and 75 dB during the off-duty phase (16:00-8:00 the next day)) for 40 days. The levels of phosphorylated tau, amyloid-β (Aβ), and neuroinflammation in the cortex and hippocampus were assessed and autophagosome (AP) aggregation was observed by transmission electron microscopy. Dyshomeostasis of autophagic flux resulting from around-the-clock noise exposure was assessed at different stages to investigate the potential pathological mechanisms. Around-the-clock noise significantly increased Aβ peptide, tau phosphorylation at Ser396 and Ser404, and neuroinflammation. Moreover, the AMPK-mTOR signaling pathway was depressed in the cortex and the hippocampus of rats exposed to around-the-clock noise. Consequently, autophagosome-lysosome fusion was deterred and resulted in AP accumulation. Our results indicate that around-the-clock noise exposure has detrimental influences on autophagic flux homeostasis and may be associated with AD-like neuropathology in the cortex and the hippocampus.

Keywords: AMPK-mTOR; Alzheimer’s disease; around-the-clock noise; autophagosome; lysosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Autophagy* / physiology
  • Homeostasis
  • Nervous System Diseases* / etiology
  • Nervous System Diseases* / pathology
  • Noise* / adverse effects
  • Rats
  • Rats, Wistar

Substances

  • Amyloid beta-Peptides

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81673136) and Scientific Research Projects (No. JK20202A020453, 20WQ042), awarded to B.C.