Neurotoxic Effects of 3.5 GHz GSM-Like RF Exposure on Cultured DRG Neurons: a Mechanistic Insight Into Oxidative and Apoptotic Pathways

Abstract

Purpose: This study investigated whether strictly non-thermal, GSM-like 3.5 GHz radiofrequency electromagnetic fields (RF-EMF)-overlapping in frequency with bands used by 5 G networks but not employing a 5 G NR waveform-disrupt redox homeostasis and activate apoptotic signaling in peripheral sensory neurons. Materials and methods: Primary mouse dorsal root ganglion (DRG) cultures were exposed in a GTEM-based setup to pulsed 3.5 GHz RF-EMF (217 Hz, similar to 12.5% duty) for 1-24 h at 37 degrees C with <0.1 degrees C temperature difference between groups. Dosimetry confirmed non-thermal exposure with localized peaks consistent with IEEE/IEC guidance. Cell viability, reactive oxygen species (ROS), mitochondrial-apoptotic markers (Bax, Bcl-2, cytochrome c, caspase-3), and p75<^>NTR were quantified by blinded confocal analysis. Results: RF-EMF caused a significant, time-dependent reduction in viability with robust ROS elevations; increased Bax and caspase-3; decreased Bcl-2; and cytochrome c release, with maximal effects at 12-24 h. p75<^>NTR upregulation indicated maladaptive neurotrophin signaling. Conclusions: Under non-thermal conditions, 3.5 GHz RF-EMF perturbs redox balance and triggers mitochondria-dependent apoptosis in DRG neurons, highlighting peripheral neuronal vulnerability to mid-band exposures. These findings provide a mechanistic link between RF exposure and oxidative/apoptotic pathways and warrant in vivo studies assessing long-term and interventional outcomes.