Rotating magnetic field improves cognitive and memory impairments in APP/PS1 mice by activating autophagy and inhibiting the PI3K/AKT/mTOR signaling pathway

Exp Neurol. 2025 Jan:383:115029. doi: 10.1016/j.expneurol.2024.115029. Epub 2024 Oct 25.

Abstract

Alzheimer's disease (AD) is a geriatric disorder that can be roughly classified into sporadic AD and hereditary AD. The latter is strongly associated with genetic factors, and its treatment poses greater challenges compared to sporadic AD. Rotating magnetic fields (RMF) is a non-invasive treatment known to have diverse biological effects, including the modulation of the central nervous system and aging. However, the impact of RMF on hereditary AD and its underlying mechanism remain unexplored. In this study, we exposed APP/PS1 mice to RMF (2 h/day, 0.2 T, 4 Hz) for a duration of 6 months. The results demonstrated that RMF treatment significantly ameliorated their cognitive and memory impairments, attenuated neuronal damage, and reduced amyloid deposition. Furthermore, RNA-sequencing analysis revealed a significant enrichment of autophagy-related genes and the PI3K/AKT-mTOR signaling pathway. Western blotting further confirmed that RMF activated autophagy and suppressed the phosphorylation of proteins associated with the PI3K/AKT/mTOR signaling pathway in APP/PS1 mice. These protective effects and the underlying mechanism were also observed in Aβ25-35-exposed HT22 cells. Collectively, our findings indicate that RMF improves cognitive and memory dysfunction in APP/PS1 mice by activating autophagy and inhibiting the PI3K/AKT/mTOR signaling pathway, thus highlighting the potential of RMF as a clinical treatment for hereditary AD.

Keywords: APP/PS1 mice; Autophagy; Hereditary Alzheimer's disease; Rotating magnetic fields; The PI3K/AKT/mTOR pathway.

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / psychology
  • Alzheimer Disease / therapy
  • Amyloid beta-Protein Precursor* / genetics
  • Animals
  • Autophagy* / drug effects
  • Autophagy* / physiology
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / therapy
  • Magnetic Field Therapy / methods
  • Male
  • Memory Disorders* / etiology
  • Memory Disorders* / therapy
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic*
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Presenilin-1 / genetics
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction* / drug effects
  • Signal Transduction* / physiology
  • TOR Serine-Threonine Kinases* / metabolism

Substances

  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Amyloid beta-Protein Precursor
  • Phosphatidylinositol 3-Kinases
  • mTOR protein, mouse
  • Presenilin-1