The recent rapid development of electronic communication techniques is resulting in a marked increase in exposure of humans to electromagnetic fields (EMFs). This has raised public concerns about the health hazards of long-term environmental EMF exposure for fetuses and children. Some studies have suggested EMF exposure in children could induce nervous system disorders. However, gender-dependent effects of microwave radiation exposure on cognitive dysfunction have not previously been reported. Here we investigated whether in utero exposure to 9.417-GHz microwave throughout gestation (Days 3.5–18) affected behavior, using the open field test (OFT), elevated-plus maze (EPM), tail suspension test (TST), forced swimming test (FST) and Morris water maze (MWM). We found that mice showed less movement in the center of an open field (using the OFT) and in an open arm (using the EPM) after in utero exposure to 9.417-GHz radiation, which suggested that the mice had increased anxiety-related behavior. Mice demonstrated reduced immobility in TST and FST after in utero exposure to 9.417-GHz radiation, which suggested that the mice had decreased depression-related behavior. From the MWM test, we observed that male offspring demonstrated decreased learning and memory, while females were not affected in learning and memory, which suggested that microwaves had gender-dependent effects. In summary, we have provided the first experimental evidence of microwaves inducing gender-dependent effects.

As wireless communication devices gain popularity, concerns about the potential risks of environmental exposure to complex frequency electromagnetic radiation (EMR) on mental health have become a public health issue. Historically, EMR research has predominantly focused on single- frequency electromagnetic waves, neglecting the study of multi-frequency electromagnetic waves, which more accurately represent everyday life. To address these concerns, our study compared the emotional effects of single-frequency and dual-frequency EMR while exploring potential molecular mechanisms and intervention targets. Our results revealed that single-frequency EMR at 2.65 or 0.8 GHz did not induce anxiety-like behavior in mice. However, exposure to dual-frequency EMR at 2.65/0.8 GHz significantly led to anxiety-like behavior in mice. Further analysis of mouse sera revealed substantial increases in corticosterone and corticotrophin releasing hormone levels following exposure to 2.65/0.8 GHz EMR. Transcriptome sequencing indicated a significant decrease in the expression of Cnr1, encoding cannabinoid receptor 1 Type (CB1R), in the cerebral. This finding was consistently verified through western blot analysis, revealing a substantial reduction in CB1R content. Additionally, a significant decrease in the endocannabinoid 2-arachidonoylglycerol was observed in the cerebral cortex. Remarkably, administering the cannabinoid receptor agonist Win55-212-2 significantly alleviated the anxiety-like behavior, and the cannabinoid receptor antagonist AM251 effectively counteracted the anti-anxiety effects of Win55-212-2. In summary, our research confirmed that dual-frequency EMR is more likely to induce anxiety-like behavior in mice than single-frequency EMR, with implications for the hypothalamic–pituitary–adrenal axis and the endocannabinoid system. Furthermore, our findings suggest that Win55-212-2 may represent a novel avenue for researching and developing anti-EMR drugs.

Background: Basolateral amygdala (BLA) deep brain stimulation (DBS) has been shown to alleviate the symptoms of post-traumatic stress disorder (PTSD), but the specific mechanisms remain incompletely understood. The hippocampus, a brain region closely connected to the amygdala, plays a key role in the pathological processes of PTSD. The N6-methyladenosine (m⁶A) methylation of RNAs in the hippocampus is known to play a significant role in regulating the brain’s response to stress and emotional disorders. Methods: This study aimed to comprehensively analyze the roles of transcriptome-wide m⁶A modifications of the hippocampus in the BLA DBS treatment of a PTSD mouse model using m⁶A sequencing. Results: Significant alterations in functional connectivity between the ventral hippocampus (vHPC) and BLA were observed in foot shock (FS) mice through functional magnetic resonance imaging (fMRI) analysis. Furthermore, we observed that the expression of the key m⁶A methyltransferase enzyme, METTL3, in the FS and BLA DBS groups was higher than that in the control group. At the same time, both FS and BLA DBS induced the widespread m⁶A methylation of RNAs in the vHPC. Gene ontology (GO) enrichment analysis revealed that FS altered methylation in metabolic, developmental, and cytoskeletal pathways, while BLA DBS targeted metabolic, cell cycle, and neuroplasticity-related genes. Additionally, BLA DBS reversed the aberrant methylation of genes associated with multiple functional pathways induced by FS, including those related to cholinergic transmission, sodium and calcium ion homeostasis, and stress hormone responsiveness. We identified a set of RNAs with methylation changes that were reversed by BLA DBS in the FS vs. Ctrl (control) comparison, including those associated with cholinergic transmission, sodium and calcium ion balance, and stress hormone response. Additionally, we detected several specific BLA DBS-related genes through MeRIP-qPCR, indicating that DBS influences crucial genes linked to calcium signaling and synaptic plasticity. Conclusions: We draw two conclusions from these findings: BLA DBS may alleviate PTSD-like symptoms by reversing FS-induced methylation changes and by altering the methylation levels of crucial genes. These findings indicate that epigenetic m⁶A modifications in the vHPC may play an important role in the amelioration of PTSD using BLA DBS.

Radiation-induced brain injury (RIBI) is one of the most common and fatal complications of cranial radiation therapy (CRT); however, no effective intervention is available currently. Metformin has been reported to have anti-RIBI activity as a first-line anti-diabetic drug. However, the mechanism of action is unclear. An RIBI mice model and an in vitro cell model under 30 and 10 Gy ⁶⁰Co γ-rays exposure were established to investigate the mechanism of metformin in RIBI. The results showed that pre-treatment with metformin protects hippocampal neurogenesis in the brain of mice and improves learning and memory ability after irradiation. Further investigations revealed that metformin pretreatment reduces inflammation and decreases DNA damage in the in vitro BV2 cell line. In addition, we observed that metformin inhibits the activation of IκB and IRF-3, which are downstream components of the cGAS-STING pathway. These findings suggest that metformin might protect the brain from RIBI, at least partly, through the cGAS pathway, making it a potential therapeutic drug for RIBI.

As mobile phones and communication base stations become more widespread, concerns have arisen regarding the potential risks of environmental exposure to multi-frequency electromagnetic radiation (EMR) and its effects on mental health. To address these concerns, our study established a dual-frequency EMR mouse model at 0.8/2.65 GHz to explore potential molecular mechanisms and intervention targets. Our results revealed that exposure to this dual-frequency EMR significantly induced anxiety-like behavior in mice. Molecular experiments further showed a significant decrease in cannabinoid receptor type 1 (CB1R) levels in the medial prefrontal cortex (mPFC) of the mice, along with a notable reduction in the endogenous cannabinoids 2-arachidonoylglycerol and anandamide. This led to a downregulation of the entire endocannabinoid system (ECS). Additional confirmation was obtained by overexpressing and knocking down CB1R in the mPFC. We found that increasing mPFC CB1R levels could effectively reduce anxiety-like behavior, while decreasing mPFC CB1R levels exacerbated it. Furthermore, we found dual-frequency EMR induced the change of ECS in the basolateral amygdala (BLA). Notably, female mice exhibited similar behavioral phenotypes and molecular mechanisms in response to dual-frequency EMR. In summary, our study demonstrates that anxiety induced by dual-frequency EMR is closely linked to the function of the ECS in the mPFC and BLA, and that CB1R expression in the mPFC plays a significant role in modulating emotional behavior in mice.