BackgroundThe widespread use of wireless devices during the last decades is raising concerns about adverse health effects of the radiofrequency electromagnetic radiation (RF‐EMR) emitted from these devices. Recent research is focusing on unraveling the underlying mechanisms of RF‐EMR and potential cellular targets. The “omics” high‐throughput approaches are powerful tools to investigate the global effects of RF‐EMR on cellular physiology.MethodsIn this work, C57BL/6 adult male mice were whole‐body exposed (nE xp = 8) for 2 hr to GSM 1800 MHz mobile phone radiation at an average electric field intensity range of 4.3–17.5 V/m or sham‐exposed (nSE = 8), and the RF‐EMR effects on the hippocampal lipidome and transcriptome profiles were assessed 6 hr later.ResultsThe data analysis of the phospholipid fatty acid residues revealed that the levels of four fatty acids [16:0, 16:1 (6c + 7c), 18:1 9c, eicosapentaenoic acid omega‐3 (EPA, 20:5 ω3)] and the two fatty acid sums of saturated and monounsaturated fatty acids (SFA and MUFA) were significantly altered (p < 0.05) in the exposed group. The observed changes indicate a membrane remodeling response of the tissue phospholipids after nonionizing radiation exposure, reducing SFA and EPA, while increasing MUFA residues. The microarray data analysis demonstrated that the expression of 178 genes changed significantly (p < 0.05) between the two groups, revealing an impact on genes involved in critical biological processes, such as cell cycle, DNA replication and repair, cell death, cell signaling, nervous system development and function, immune system response, lipid metabolism, and carcinogenesis.ConclusionsThis study provides preliminary evidence that mobile phone radiation induces hippocampal lipidome and transcriptome changes that may explain the brain proteome changes and memory deficits previously shown by our group.