The GR of CA1 is involved in anxiety-like behavior induced by 0.8/2.65 GHz dual-frequency electromagnetic radiation

The proliferation of wireless communication has increased environmental exposure to complex radiofrequency electromagnetic radiation (EMR), sparking concerns about its impact on brain function and emotional regulation. Most studies use single-frequency paradigms that do not reflect real-world multifrequency exposure.

We developed a dual-frequency EMR mouse model (0.8/2.65 GHz, 4 W/kg, 4 h/day for 21 days) to evaluate behavioral, endocrine, neurophysiological, and molecular outcomes.

Dual-frequency EMR induced anxiety-like behaviors without depression-like phenotypes, accompanied by hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis. Molecular analysis showed selective downregulation of glucocorticoid receptors (GRs) in the hippocampal CA1 region, while mineralocorticoid receptors (MR) and FKBP51 remained unchanged. GR overexpression in CA1 alleviated anxiety-like behavior, whereas GR knockdown exacerbated it and increased corticosterone levels. Effects were consistent in male and female mice, but functional validations were limited to males.

Our findings indicate that CA1 GR signaling may mediate the link between dual-frequency EMR exposure, HPA axis dysregulation, and anxiety-like behavior, suggesting GR restoration as a potential therapeutic target for EMR-induced emotional disturbances.