AbstractBackgroundWith the development of communication technology, the public is paying increasing attention to whether electromagnetic radiation is harmful to health. Mobile phone communication has entered the 5G era, and there are almost no reports on electromagnetic radiation at 2650 MHz. Therefore, it is necessary to evaluate the risk of adverse effects of 5G mobile phone EMR exposure on the human brain.MethodsMale animals were continuously exposed to 2650 MHz‐EMR for 28 days with a whole‐body averaged specific absorption rate (WBSAR) of 2.06 W/kg for 4 h per day. Mouse behavior was assessed using the open‐field test (OFT), elevated‐plus maze (EPM), and tail suspension test (TST). The Morris water maze (MWM), HE staining, and TUNEL staining were used to evaluate the spatial memory ability and pathological morphology of hippocampal dentate gyrus cells. Additionally, the expression levels of brain‐derived neurotrophic factor (BDNF), aminobutyric acid (GABA), and glucocorticoid (GR) in the hippocampus were detected by western blotting and immunohistochemistry, while the corticosterone (CORT) level in serum was detected by ELISA.ResultsIn the OFT, the total distance traveled, central distance traveled, and residence time significantly decreased in the EMR exposure group (p< .05). In EPM, the percentage of the number of times to open the arm and the percentage of time to open the arm significantly decreased in the EMR exposure group. However, in the TST, the two groups had no significant difference in the 4‐min immobility time. In the MWM, the escape latency of the EMR exposure group was shorter than that of the control group, with no significant difference. Furthermore, CORT levels in serum were significantly increased in the EMR exposure group (p< .05), while the expression of BDNF and GR proteins in the hippocampus was reduced (p< .05), but there was no significant difference in GABA expression.ConclusionsOur results indicate that exposure to 2650 MHz‐EMR (WBSAR: 2.06 W/kg, 28 days, 4 h per day) had no significant effect on the spatial memory ability of mice (in comparison to little effect). The exposure may be associated with anxiety‐like behavior in mice but not related to depression‐like behavior in mice.