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Functional Interrogation of Adult Hypothalamic Neurogenesis with Focal Radiological Inhibition
Published on: November 14, 2013
Long-term radiofrequency electromagnetic fields exposure attenuates cognitive dysfunction in 5×FAD mice by regulating
Yeonghoon Son1, Hye-Jin Park1, Ye Ji Jeong1
1Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul, Korea.
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.
Insights
Long-term radiofrequency electromagnetic fields exposure in Alzheimer
Area of Science:
- Neuroscience
- Biomedical Engineering
- Alzheimer's Disease Research
Background:
- Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) deposition and glial activation.
- Microglia play a crucial role in AD pathogenesis, with their activation contributing to neuroinflammation.
- Previous studies indicated radiofrequency electromagnetic fields (RF-EMF) may reduce Aβ deposition and glial activation in 5×FAD mice.
Purpose of the Study:
- To investigate if the therapeutic effects of RF-EMF in 5×FAD mice are mediated by regulating activated microglia.
- To analyze microglial gene expression profiles and the presence of microglia in the brain following RF-EMF exposure.
- To compare the effects of RF-EMF with a colony-stimulating factor 1 receptor (CSF1R) inhibitor on microglial activity.
Main Methods:
- 5×FAD mice were exposed to 1950 MHz RF-EMF (5 W/kg) for 6 months.
- Behavioral tests (object recognition, Y-maze) and molecular/histopathological analyses were performed.
- Gene expression analysis of microglial markers (Iba1, CSF1R) and related pathways was conducted, comparing RF-EMF and CSF1R inhibitor (PLX3397) groups.
Main Results:
- Six months of RF-EMF exposure ameliorated cognitive impairment and reduced Aβ deposition in 5×FAD mice.
- RF-EMF exposure significantly reduced the expression of Iba1 and CSF1R in the hippocampus.
- Both RF-EMF and PLX3397 suppressed genes associated with microgliosis (Csf1r, CD68, Ccl6) and pro-inflammatory interleukin-1β, as well as microglial function genes (Trem2, Fcgr1a, Ctss, Spi1).
Conclusions:
- Long-term RF-EMF exposure effectively ameliorates Aβ pathology and cognitive deficits in a mouse model of Alzheimer's disease.
- The therapeutic effects are linked to the suppression of amyloid-beta deposition-induced microgliosis.
- RF-EMF acts by targeting the CSF1R pathway, a key regulator of microglial activation and proliferation.
