1,800 MHz Radiofrequency Electromagnetic Irradiation Impairs Neurite Outgrowth With a Decrease in Rap1-GTP in Primary Mouse Hippocampal Neurons and Neuro2a Cells

Abstract

Background: With the global popularity of communication devices such as mobile phones, there are increasing concerns regarding the effect of radiofrequency electromagnetic radiation (RF-EMR) on the brain, one of the most important organs sensitive to RF-EMR exposure at 1,800 MHz. However, the effects of RF-EMR exposure on neuronal cells are unclear. Neurite outgrowth plays a critical role in brain development, therefore, determining the effects of 1,800 MHz RF-EMR exposure on neurite outgrowth is important for exploring its effects on brain development.Objectives: We aimed to investigate the effects of 1,800 MHz RF-EMR exposure for 48 h on neurite outgrowth in neuronal cells and to explore the associated role of the Rap1 signaling pathway.Material and Methods: Primary hippocampal neurons from C57BL/6 mice and Neuro2a cells were exposed to 1,800 MHz RF-EMR at a specific absorption rate (SAR) value of 4 W/kg for 48 h. CCK-8 assays were used to determine the cell viability after 24, 48, and 72 h of irradiation. Neurite outgrowth of primary hippocampal neurons (DIV 2) and Neuro2a cells was observed with a 20 × optical microscope and recognized by ImageJ software. Rap1a and Rap1b gene expressions were detected by real-time quantitative PCR. Rap1, Rap1a, Rap1b, Rap1GAP, and p-MEK1/2 protein expressions were detected by western blot. Rap1-GTP expression was detected by immunoprecipitation. The role of Rap1-GTP was assessed by transfecting a constitutively active mutant plasmid (Rap1-Gly_Val-GFP) into Neuro2a cells.Results: Exposure to 1,800 MHz RF-EMR for 24, 48, and 72 h at 4 W/kg did not influence cell viability. The neurite length, primary and secondary neurite numbers, and branch points of primary mouse hippocampal neurons were significantly impaired by 48-h RF-EMR exposure. The neurite-bearing cell percentage and neurite length of Neuro2a cells were also inhibited by 48-h RF-EMR exposure. Rap1 activity was inhibited by 48-h RF-EMR with no detectable alteration in either gene or protein expression of Rap1. The protein expression of Rap1GAP increased after 48-h RF-EMR exposure, while the expression of p-MEK1/2 protein decreased. Overexpression of constitutively active Rap1 reversed the decrease in Rap1-GTP and the neurite outgrowth impairment in Neuro2a cells induced by 1,800 MHz RF-EMR exposure for 48 h.Conclusion: Rap1 activity and related signaling pathways are involved in the disturbance of neurite outgrowth induced by 48-h 1,800 MHz RF-EMR exposure. The effects of RF-EMR exposure on neuronal development in infants and children deserve greater focus.

Central Causation of Autism/ASDs via Excessive [Ca2+]i Impacting Six Mechanisms Controlling Synaptogenesis during the Perinatal Period: The Role of Electromagnetic Fields and Chemicals and the NO/ONOO(-) Cycle, as Well as Specific Mutations

“…It has also been shown that low-intensity EMF exposures act on neural stem cells to inhibit neurite outgrowth [115][116][117][118][119][120]. Because such neurite outgrowth is an essential precursor process for synaptogenesis, such effects may be predicted to greatly lower synapse formation in the developing brain.…”

1.7 GHz long-term evolution radiofrequency electromagnetic field with stable power monitoring and efficient thermal control has no effect on the proliferation of various human cell types

“…However, these researchers also demonstrated that exposure to 1.8 GHz RF-EMF at a SAR of 4 W/Kg did not elicit DNA damage [10]. Li et al reported that exposures to 1.8 GHz RF-EMF at a SAR of 4 W/kg for 48 h did not affect cell viability but impaired neurite outgrowth in primary mouse hippocampal neurons and Neuro2a cells [11] Other studies have reported that RF-EMFs have no effects on mitochondrial function and did not induce apoptosis or chromosomal alterations; exposure to 1.95 GHz RF-EMF ranging from 0 to 4 W/Kg for up to 66 h did not induce apoptosis, oxidative stress, or DNA damage in human hematopoietic stem cells or the human leukemia cell line, HL-60 [12]. Intermittent exposure (5 min on/30 min off) to a SAR of 1.5 W/Kg 1.71 GHz RF-EMF did not induce any significant cellular dysfunction in mouse embryonic stem cell-derived neural progenitor cells [13].…”

“…Li et al . reported that exposures to 1.8 GHz RF-EMF at a SAR of 4 W/kg for 48 h did not affect cell viability but impaired neurite outgrowth in primary mouse hippocampal neurons and Neuro2a cells [ 11 ]…”

Paternal Radiofrequency Electromagnetic Radiation Exposure Causes Sex-Specific Differences in Body Weight Trajectory and Glucose Metabolism in Offspring Mice

“…Nowadays, non-ionizing radiofrequency electromagnetic radiation (RF-EMR) is ubiquitous, especially in the industry, military, radio, and wireless communications sectors. The potential adverse effects of RF-EMR on human health and offspring development have obtained lots of public attention (1)(2)(3)(4). Notably, the International Agency for Research on Cancer (IARC) has categorized RF-EMR as possible carcinogens to humans (5,6).…”