The endocannabinoid system is involved in the anxiety-like behavior induced by dual-frequency 2.65/0.8 GHz electromagnetic radiation in mice

Teng Xue; Rui-Han Ma; Chou Xu; Bin Sun; Dong-Fei Yan; Xiao-Man Liu; Dawen Gao; Zhi-Hui Li; Yan Gao; Chang-Zhen Wang

doi:10.3389/fnmol.2024.1366855

The endocannabinoid system is involved in the anxiety-like behavior induced by dual-frequency 2.65/0.8 GHz electromagnetic radiation in mice

Front Mol Neurosci. 2024 Apr 15:17:1366855. doi: 10.3389/fnmol.2024.1366855. eCollection 2024.

Authors

Teng Xue^#^{1

2}, Rui-Han Ma^#^{1

2}, Chou Xu^#^{3

4}, Bin Sun¹, Dong-Fei Yan¹, Xiao-Man Liu¹, Dawen Gao⁵, Zhi-Hui Li¹, Yan Gao⁵, Chang-Zhen Wang¹

Affiliations

¹ Laboratory of Bioelectromagnetics, Beijing Institute of Radiation and Medicine, Beijing, China.
² School of Life Sciences, Hebei University, Baoding, Hebei, China.
³ Department of Critical Care Medicine, The 983rd Hospital of the Joint Logistics Support Force of PLA, Tianjin, China.
⁴ Chinese PLA General Hospital, Beijing, China.
⁵ Center of Cognition and Brain Science, Beijing Institute of Basic Medical Sciences, Beijing, China.

^# Contributed equally.

Abstract

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.

Keywords: 0.8 GHz; 2.65 GHz; anxiety-like behavior; cerebral cortex; electromagnetic radiation; endocannabinoid system.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by National Science and Technology Innovation 2030 Major Program 2021ZD0200900.