1800 MHz Radiofrequency Electromagnetic Field Impairs Neurite Outgrowth Through Inhibiting EPHA5 Signaling

Chen, Chunhai; Ma, Qinglong; Deng, Ping; Lin, Min; Gao, Peng; He, Mindi; Lu, Yonghui; Pi, Huifeng; He, Zhaoren; Zhou, Chao; Zhang, Yanwen; Yu, Zhengping; Zhang, Lei

doi:10.3389/fcell.2021.657623

Cited by 5 publications

(9 citation statements)

References 78 publications

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“…The activity and density of mature spines in primary hippocampal neurons decrease significantly when exposed to 2.4 W/kg RF-EMR, and the average length of dendrites per neuron is also reduced ( 14 ). We also showed that RF-EMR exposure impairs neurite outgrowth in neural stem cell-derived neurons ( 15 , 16 ). However, a study using a pulsed radiofrequency electromagnetic field reported that it can potentiate neurite outgrowth in the dopaminergic MN9D cell line ( 17 ).…”

Section: Introductionmentioning

confidence: 65%

“…Kim et al reported that the total number of dendritic spines was significantly decreased in hippocampal neurons after RF-EMR exposure at 4 W/kg for 4 weeks ( 9 ). Our previous studies also showed that 72 h of 1,800 MHz RF-EMR exposure significantly inhibited neurite outgrowth in embryonic neural stem cells (eNSCs) at 4 W/kg, in which the BHLH gene and the EPHA5 signaling pathway were involved ( 15 , 16 ). The mechanisms underlying the effects of RF-EMR exposure on neurite outgrowth or synaptic plasticity are thought to include changes in calcium ion channels, the myelin sheath, oxidative stress and the glutamate receptor signaling pathway ( 36 , 41 , 42 ).…”

Section: Discussionmentioning

confidence: 89%

“…Primary mouse hippocampal neurons and Neuro2a cells were irradiated in an sXc-1800 exposure system (IT'IS Foundation, Zurich, Switzerland) using the irradiation method introduced in previous studies ( 15 , 16 ). RF-EMR exposure system is mainly composed of the following four parts: narrowband amplifier, arbitrary function generator, RF generator, and two waveguide.…”

Section: Methodsmentioning

confidence: 99%

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

Deng

Chen

et al. 2021

Front. Public Health

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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.

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Section: Introductionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

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

Deng

Chen

et al. 2021

Front. Public Health

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“…The biological effects of exposure to EMFs have been investigated in several studies, particularly in experimental mouse studies 10 . However, the biological effects of such exposure on the development of the brain and the underlying mechanisms have still not been completely elucidated 2 .…”

Section: Discussionmentioning

confidence: 99%

“…The usage of wireless communication devices has become a ubiquitous part of daily personal and professional life 1 , resulting in an augmented public exposure to radiofrequency electromagnetic radiation (RF-EMF) 2 . Long-term exposure to RF-EMF emitted by various electronic devices has been propounded to result in hazardous biological and health effects 3 .…”

Section: Introductionmentioning

confidence: 99%

Impressions of the chronic 900-MHz electromagnetic field in the prenatal period on Purkinje cells in male rat pup cerebella: is it worth mentioning?

Baş

Şengül

Bas

et al. 2022

Rev. Assoc. Med. Bras.

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OBJECTIVE:The aim of this study was to examine the changes on the Purkinje cells in the cerebella of male rat pups born to pregnant dams that were exposed to an electromagnetic field in the prenatal period. METHODS:The first stage of the study involved 12 Sprague-Dawley rats, 6 male and 6 female, weighing between 180 and 250 g. The female rats in the experimental group were exposed to a 900-MHz electromagnetic field for 1 h at the same time every day, and no procedure was performed on the control group. Following pregnancy, six male pups from each group were divided into experimental and control groups without any procedure on the pups. After 2 months, they were sacrificed and their cerebella were removed. Histopathologically, following routine processing and fixation procedures, the cerebella were embedded in the tissue blocks. The sections taken from these blocks were stained with cresyl violet. The Purkinje cells in the cerebella were then counted on sections using the optical dissector method on an image analysis system. RESULTS: The estimation of number of the Purkinje cells in the groups revealed more cells in rats in the control group than in the experimental group. Histopathologically, Purkinje cells exhibited a normal morphological structure in the control group, while the cells in the experimental group showed damage. CONCLUSIONS: It might be asserted that the exposure of mothers to an electromagnetic field in the prenatal period may affect the development of Purkinje cells in the pup cerebella.

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Transcriptional response of primary hippocampal neurons following exposure to 3.0 GHz radiofrequency electromagnetic fields

Cantu,

Butterworth,

Payne

et al. 2024

Bioelectromagnetics

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Exposure to radiofrequency (RF) electromagnetic fields (EMF) has been associated with the modulation of neuronal electrophysiology and synaptic plasticity. Given the potential of these changes to coincide with alterations in gene expression, this study investigated whether a transcriptional response would occur in neurons following exposure to RF‐EMF, under both thermal and nonthermal conditions. Rat primary hippocampal neurons (PHNs) underwent either a single (one‐time) or a multiple (3‐times, once a day) exposures to RF‐EMF (3.0 GHz, CW) at two different mean specific absorption rate (SAR) values of 0.57 W/kg or 5.91 W/kg, which induced a temperature change (ΔT °C) of approximately 0.3°C or 3.6°C, respectively. Alteration in transcription in the RF‐EMF‐exposed PHNs versus the sham counterparts was assessed at 0, 4, and 24 h postexposure via high‐throughput RNA sequencing using Illumina HiSeq. 2000. A total of 20 differentially expressed genes (DEGs) exhibited significant upregulation due to RF‐EMF exposure, observed only with the high SAR dose that induced a thermal rise. However, the expression of these DEGs was not significant at 24 h postexposure. Our findings confirmed a lack of nonthermal effects on gene expression under low RF‐EMF exposure conditions as evaluated. Additionally, the results indicated a slight thermal effect of exposures at the dose nearing the standards threshold of 4 W/kg; however, the effect appeared to be transient. The study suggests that RF‐EMF exposures at a level close to the standards threshold, despite inducing mild temperature elevations (i.e., 3–5°C above normal), would not trigger biologically critical cellular changes.

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1800 MHz Radiofrequency Electromagnetic Field Impairs Neurite Outgrowth Through Inhibiting EPHA5 Signaling

Cited by 5 publications

References 78 publications

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

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

Impressions of the chronic 900-MHz electromagnetic field in the prenatal period on Purkinje cells in male rat pup cerebella: is it worth mentioning?

Transcriptional response of primary hippocampal neurons following exposure to 3.0 GHz radiofrequency electromagnetic fields

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