Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (11): 2497-2503.doi: 10.4103/1673-5374.371379

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Long-term radiofrequency electromagnetic fields exposure attenuates cognitive dysfunction in 5×FAD mice by regulating microglial function

Yeonghoon Son1, #, Hye-Jin Park1, #, Ye Ji Jeong1, #, Hyung-Do Choi2, Nam Kim3, Hae-June Lee1, *   

  1. 1Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul, Korea; 2Department of EMF Research Team, Radio and Broadcasting Technology Laboratory, Electronics and Telecommunications Research Institute, Daejon, Korea; 3School of Electrical and Computer Engineering, Chungbuk National University, Cheongju, Korea
  • Online:2023-11-15 Published:2023-05-05
  • Contact: Hae-June Lee, DVM, PhD, hjlee@kirams.re.kr.
  • Supported by:
    This work was supported by Institute of Information & Communications Technology Planning & Evaluation (IITP) grant funded by Korea government (MSIT), Nos. 2017-0-00961 and 2019-0-00102 (to HDC).

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Abstract: We have previously found that long-term effects of exposure to radiofrequency electromagnetic fields in 5×FAD mice with severe late-stage Alzheimer’s disease reduced both amyloid-β deposition and glial activation, including microglia. To examine whether this therapeutic effect is due to the regulation of activated microglia, we analyzed microglial gene expression profiles and the existence of microglia in the brain in this study. 5×FAD mice at the age of 1.5 months were assigned to sham- and radiofrequency electromagnetic fields-exposed groups and then animals were exposed to 1950 MHz radiofrequency electromagnetic fields at a specific absorption rate of 5 W/kg for 2 hours/day and 5 days/week for 6 months. We conducted behavioral tests including the object recognition and Y-maze tests and molecular and histopathological analysis of amyloid precursor protein/amyloid-beta metabolism in brain tissue. We confirmed that radiofrequency electromagnetic field exposure for 6 months ameliorated cognitive impairment and amyloid-β deposition. The expression levels of Iba1 (pan-microglial marker) and colony-stimulating factor 1 receptor (CSF1R; regulates microglial proliferation) in the hippocampus in 5×FAD mice treated with radiofrequency electromagnetic fields were significantly reduced compared with those of the sham-exposed group. Subsequently, we analyzed the expression levels of genes related to microgliosis and microglial function in the radiofrequency electromagnetic fields-exposed group compared to those of a CSF1R inhibitor (PLX3397)-treated group. Both radiofrequency electromagnetic fields and PLX3397 suppressed the levels of genes related to microgliosis (Csf1r, CD68, and Ccl6) and pro-inflammatory cytokine interleukin-1β. Notably, the expression levels of genes related to microglial function, including Trem2, Fcgr1a, Ctss, and Spi1, were decreased after long-term radiofrequency electromagnetic field exposure, which was also observed in response to microglial suppression by PLX3397. These results showed that radiofrequency electromagnetic fields ameliorated amyloid-β pathology and cognitive impairment by suppressing amyloid-β deposition-induced microgliosis and their key regulator, CSF1R.

Key words: 5×FAD, Alzheimer’s disease, CSF1R,  , long term exposure, microglial function, neuroinflammation, radiofrequency electromagnetic fields, therapeutic effect