Microwave Radiation Caused Dynamic Metabolic Fluctuations in the Mammalian Hippocampus.

To investigate the dynamic changes in hippocampal metabolism after microwave radiation using liquid chromatography in tandem with mass spectrometry/mass spectrometry (LC-MS/MS) and to identify potential biomarkers. Wistar rats were randomly assigned to a sham group and a microwave radiation group. The rats in the microwave radiation group were exposed to 2.856 GHz for 15 min for three times, with 5 min intervals. The rats in the sham group were not exposed. Transmission electron microscope revealed blurring of the synaptic cleft and postsynaptic dense thickening in hippocampal neurons after microwave radiation. Metabolomic analysis revealed 38, 24, and 39 differentially abundant metabolites at 3, 7, and 14 days after radiation, respectively, and the abundance of 9 metabolites, such as argininosuccinic acid, was continuously decreased. After microwave radiation, the abundance of metabolites such as argininosuccinic acid was successively decreased, indicating that these metabolites could be potential biomarkers for hippocampal tissue injury.

Research progress in the effects of terahertz waves on biomacromolecules.

With the rapid development of terahertz technologies, basic research and applications of terahertz waves in biomedicine have attracted increasing attention. The rotation and vibrational energy levels of biomacromolecules fall in the energy range of terahertz waves; thus, terahertz waves might interact with biomacromolecules. Therefore, terahertz waves have been widely applied to explore features of the terahertz spectrum of biomacromolecules. However, the effects of terahertz waves on biomacromolecules are largely unexplored. Although some progress has been reported, there are still numerous technical barriers to clarifying the relation between terahertz waves and biomacromolecules and to realizing the accurate regulation of biological macromolecules by terahertz waves. Therefore, further investigations should be conducted in the future. In this paper, we reviewed terahertz waves and their biomedical research advantages, applications of terahertz waves on biomacromolecules and the effects of terahertz waves on biomacromolecules. These findings will provide novel ideas and methods for the research and application of terahertz waves in the biomedical field.

Establishment of injury models in studies of biological effects induced by microwave radiation.

Microwave radiation has been widely used in various fields, such as communication, industry, medical treatment, and military applications. Microwave radiation may cause injuries to both the structures and functions of various organs, such as the brain, heart, reproductive organs, and endocrine organs, which endanger human health. Therefore, it is both theoretically and clinically important to conduct studies on the biological effects induced by microwave radiation. The successful establishment of injury models is of great importance to the reliability and reproducibility of these studies. In this article, we review the microwave exposure conditions, subjects used to establish injury models, the methods used for the assessment of the injuries, and the indicators implemented to evaluate the success of injury model establishment in studies on biological effects induced by microwave radiation.

Low p-SYN1 (Ser-553) Expression Leads to Abnormal Neurotransmitter Release of GABA Induced by Up-Regulated Cdk5 after Microwave Exposure: Insights on Protection and Treatment of Microwave-Induced Cognitive Dysfunction.

With the wide application of microwave technology, concerns about its health impact have arisen. The signal transmission mode of the central nervous system and neurons make it particularly sensitive to electromagnetic exposure. It has been reported that abnormal release of amino acid neurotransmitters is mediated by alteration of p-SYN1 after microwave exposure, which results in cognitive dysfunction. As the phosphorylation of SYN1 is regulated by different kinases, in this study we explored the regulatory mechanisms of SYN1 fluctuations following microwave exposure and its subsequent effect on GABA release, aiming to provide clues on the mechanism of cognitive impairment caused by microwave exposure. In vivo studies with Timm and H&E staining were adopted and the results showed abnormality in synapse formation and neuronal structure, explaining the previously-described deficiency in cognitive ability caused by microwave exposure. The observed alterations in SYN1 level, combined with the results of earlier studies, indicate that SYN1 and its phosphorylation status (ser-553 and ser62/67) may play a role in the abnormal release of neurotransmitters. Thus, the role of Cdk5, the upstream kinase regulating the formation of p-SYN1 (ser-553), as well as that of MEK, the regulator of p-SYN1 (ser-62/67), were investigated both in vivo and in vitro. The results showed that Cdk5 was a negative regulator of p-SYN1 (ser-553) and that its up-regulation caused a decrease in GABA release by reducing p-SYN1 (ser-553). While further exploration still needed to elaborate the role of p-SYN1 (ser-62/67) for neurotransmitter release, MEK inhibition had was no impact on p-Erk or p-SYN1 (ser-62/67) after microwave exposure. In conclusion, the decrease of p-SYN1 (ser-553) may result in abnormalities in vesicular anchoring and GABA release, which is caused by increased Cdk5 regulated through Calpain-p25 pathway after 30 mW/cm2 microwave exposure. This study provided a potential new strategy for the prevention and treatment of microwave-induced cognitive dysfunction.

Dose-dependent Cardiac Dysfunction and Structural Damage in Rats after Shortwave Radiation.

OBJECTIVE: To detect the effects of shortwave radiation on dose-dependent cardiac structure and function in rats after radiation and to elucidate the mechanism of shortwave radiation induced cardiac injury to identify sensitive indicators and prophylactic treatment. METHODS: One hundred Wistar rats were either exposed to 27 MHz continuous shortwave at a power density of 5, 10, and 30 mW/cm 2 for 6 min or undergone sham exposure for the control (the rats had to be placed in the exposure system with the same schedules as the exposed animals, but with an inactive antenna). The Ca 2+, glutamic oxaloacetic transaminase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) content in the peripheral serum of the rats were detected by an automatic blood biochemical analyser. The electrocardiogram (ECG) of standard lead II was recorded by a multi-channel physiological recording and analysis system. The cardiac structure of rats was observed by light and electron microscopy. RESULTS: The results showed that the 5, 10, and 30 mW/cm 2 shortwave radiation caused a significant increased in the levels of Ca 2+, AST, CK, and LDH in the peripheral serum of rats. The cardiac structure was damaged by radiation and showed a disordered arrangement of myocardial fibres, the cavitation and swelling of myocardial mitochondria. These injuries were most significant 7 d after radiation and were not restored until 28 d after radiation. CONCLUSION: Shortwave radiation of 5, 10, and 30 mW/cm 2 can damage rat cardiac function, including damage to the tissue structure and ultrastructure, especially at the level of the myocardial fibres and mitochondria. Shortwave radiation at 5, 10, and 30 mW/cm 2 induced damage to rat heart function and structure with a dose-effect relationship, i.e., the greater the radiation dose was, the more significant the damage was.

Exposure Effects of Terahertz Waves on Primary Neurons and Neuron-like Cells Under Nonthermal Conditions.

OBJECTIVE: This study aimed to explore the potential effects of terahertz (THz) waves on primary cultured neurons from 4 rat brain regions (hippocampus, cerebral cortex, cerebellum, and brainstem) and 3 kinds of neuron-like cells (MN9D, PC12, and HT22 cells) under nonthermal conditions. METHODS: THz waves with an output power of 50 (0.16 THz) and 10 (0.17 THz) mW with exposure times of 6 and 60 min were used in this study. Analysis of temperature change, neurite growth, cell membrane roughness, micromorphology, neurotransmitters and synaptic-related proteins (SYN and PSD95) was used to evaluate the potential effects. RESULTS: Temperature increase caused by the THz wave was negligible. THz waves induced significant neurotransmitter changes in primary hippocampal, cerebellar, and brainstem neurons and in MN9D and PC12 cells. THz wave downregulated SYN expression in primary hippocampal neurons and downregulated PSD95 expression in primary cortical neurons. CONCLUSION: Different types of cells responded differently after THz wave exposure, and primary hippocampal and cortical neurons and MN9D cells were relatively sensitive to the THz waves. The biological effects were positively correlated with the exposure time of the THz waves.

The specific absorption rate in different brain regions of rats exposed to electromagnetic plane waves.

Accurate dosimetry of a specific brain region in rats exposed to an electromagnetic field (EMF) is essential for studies focusing on dose-effect relationship of the region. However, only dosimetry of whole brain or whole body were evaluated in most of previous studies. In this study, a numerical voxel rat model with 10 segmented brain regions was constructed. Then, the effects of frequency, incidence direction, and E-polarization direction of plane wave EMF on brain region averaged specific absorption rate (BRSAR) of rats were investigated. At last, the reliability of using whole-body averaged SAR (WBDSAR) and whole-brain averaged SAR (WBRSAR) as estimations of BRSAR were also evaluated. Our results demonstrated that the BRSAR depended on the frequency, incidence direction, and E-polarization direction of the EMF. Besides, the largest deviation could be up to 13.1 dB between BRSAR and WBDSAR and 9.59 dB between BRSAR and WBRSAR. The results suggested that to establish an accurate dose-effect relationship, the variance of the BRSAR induced by alteration of frequency, incidence direction, and E-polarization direction of EMF should be avoided or carefully evaluated. Furthermore, the use of WBDSAR and WBRSAR as estimations of BRSAR should be restricted to certain conditions such that the deviations are not too large.

A novel microcurrent dressing for wound healing in a rat skin defect model.

BACKGROUND: The exogenous application of low-intensity electric stimulation (ES) may mimic a natural endogenous bioelectric current and accelerate the repair process of skin wounds. This study designed a novel microcurrent dressing (MCD) and evaluated its potential effects on wound healing in a rat skin defect model. METHODS: First, wireless ES was integrated into a medical cotton cushion to fabricate the MCD, and its electrical property was examined by using a universal power meter. Then, animal experiments were conducted to evaluate the MCD's effect. Forty-five rats were randomized into control (Con) group, Vaseline gauze (VG) group and MCD group. A full-thickness round skin incision 1.5 cm in diameter was made on the back of each animal. Apart from routine disinfection, the Con rats were untreated, whereas the other two groups were treated with VG or MCD. On days 3, 7 and 14 post injury, the wound areas were observed and measured using image analysis software following photography, and the skin samples were harvested from wound tissue. Then, histopathological morphology was observed routinely by hematoxylin and eosin (HE) staining; tumor necrosis factor α (TNF-α) and interleukin (IL)-1ß expression were detected by Western blotting. Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) expression were detected with immunohistochemistry. RESULTS: The MCD generated a sf electric potential greater than 0.95 V. Animal experiments showed that the wound-healing rate in the MCD group was significantly increased compared with the Con and VG groups (P < 0.05 or P < 0.01). Histopathological observation revealed an alleviated inflammatory response, induced vascular proliferation and accelerated epithelization in the MCD group. Moreover, samples from the MCD group expressed reduced TNF-α and IL-1ß levels and increased VEGF and EGF levels compared with those of the other two groups (P < 0.05 or P < 0.01). However, no significant difference was noted between the Con and VG groups at each time point. CONCLUSIONS: The MCD generates a stable and lasting ES and significantly promotes wound healing by reducing inflammation duration and increasing growth factors expression. Thus, MCD may act as a promising biomaterial device for skin wound healing.

Behavioral Abnormality along with NMDAR-related CREB Suppression in Rat Hippocampus after Shortwave Exposure.

OBJECTIVE: To estimate the detrimental effects of shortwave exposure on rat hippocampal structure and function and explore the underlying mechanisms. METHODS: One hundred Wistar rats were randomly divided into four groups (25 rats per group) and exposed to 27 MHz continuous shortwave at a power density of 5, 10, or 30 mW/cm2 for 6 min once only or underwent sham exposure for the control. The spatial learning and memory, electroencephalogram (EEG), hippocampal structure and Nissl bodies were analysed. Furthermore, the expressions of N-methyl-D-aspartate receptor (NMDAR) subunits (NR1, NR2A, and NR2B), cAMP responsive element-binding protein (CREB) and phosphorylated CREB (p-CREB) in hippocampal tissue were analysed on 1, 7, and 14 days after exposure. RESULTS: The rats in the 10 and 30 mW/cm2 groups had poor learning and memory, disrupted EEG oscillations, and injured hippocampal structures, including hippocampal neurons degeneration, mitochondria cavitation and blood capillaries swelling. The Nissl body content was also reduced in the exposure groups. Moreover, the hippocampal tissue in the 30 mW/cm2 group had increased expressions of NR2A and NR2B and decreased levels of CREB and p-CREB. CONCLUSION: Shortwave exposure (27 MHz, with an average power density of 10 and 30 mW/cm2) impaired rats' spatial learning and memory and caused a series of dose-dependent pathophysiological changes. Moreover, NMDAR-related CREB pathway suppression might be involved in shortwave-induced structural and functional impairments in the rat hippocampus.

Real-time Microwave Exposure Induces Calcium Efflux in Primary Hippocampal Neurons and Primary Cardiomyocytes.

OBJECTIVE: To detect the effects of microwave on calcium levels in primary hippocampal neurons and primary cardiomyocytes by the real-time microwave exposure combined with laser scanning confocal microscopy. METHODS: The primary hippocampal neurons and primary cardiomyocytes were cultured and labeled with probes, including Fluo-4 AM, Mag-Fluo-AM, and Rhod-2, to reflect the levels of whole calcium [Ca2+], endoplasmic reticulum calcium [Ca2+]ER, and mitochondrial calcium [Ca2+]MIT, respectively. Then, the cells were exposed to a pulsed microwave of 2.856 GHz with specific absorption rate (SAR) values of 0, 4, and 40 W/kg for 6 min to observe the changes in calcium levels. RESULTS: The results showed that the 4 and 40 W/kg microwave radiation caused a significant decrease in the levels of [Ca2+], [Ca2+]ER, and [Ca2+]MIT in primary hippocampal neurons. In the primary cardiomyocytes, only the 40 W/kg microwave radiation caused the decrease in the levels of [Ca2+], [Ca2+]ER, and [Ca2+]MIT. Primary hippocampal neurons were more sensitive to microwave exposure than primary cardiomyocytes. The mitochondria were more sensitive to microwave exposure than the endoplasmic reticulum. CONCLUSION: The calcium efflux was occurred during microwave exposure in primary hippocampal neurons and primary cardiomyocytes. Additionally, neurons and mitochondria were sensitive cells and organelle respectively.

HIF-1α regulates COXIV subunits, a potential mechanism of self-protective response to microwave induced mitochondrial damages in neurons.

Anxiety and speculation about potential health hazards of microwaves exposure are spreading in the past decades. Hypoxia-inducible factor-1α (HIF-1α), which can be activated by reactive oxygen species (ROS), played pivotal roles in protective responses against microwave in neuron-like cells. In this study, we established 30 mW/cm2 microwave exposed animal model, which could result in revisable injuries of neuronal mitochondria, including ultrastructure and functions, such as ROS generation and cytochrome c oxidase (COX) activity. We found that the ratio of COXIV-1/COXIV-2, two isoforms of COXIV, decreased at 1 d and increased from 3 d to 14 d. Similar expression changes of HIF-1α suggested that COXIV-1 and COXIV-2 might be regulated by HIF-1α. In neuron-like cells, 30 mW/cm2 microwave down-regulated COX activity from 30 min to 6 h, and then started to recover. And, both HIF-1α transcriptional activity and COXIV-1/COXIV-2 ratio were up-regulated at 6 h and 9 h after exposure. Moreover, HIF-1α inhibition down-regulated COXIV-1 expression, promoted ROS generation, impaired mitochondrial membrane potentials (MMP), as well as abolished microwave induced ATP production. In conclusion, microwave induced mitochondrial ROS production activated HIF-1α and regulated COXIV-1 expression to restore mitochondria functions. Therefore, HIF-1α might be a potential target to impair microwave induced injuries.

Microwave radiation leading to shrinkage of dendritic spines in hippocampal neurons mediated by SNK-SPAR pathway.

The popularization of microwave raised concerns about its influence on health including cognitive function which is associated greatly with dendritic spines plasticity. SNK-SPAR is a molecular pathway for neuronal homeostatic plasticity during chronically elevated activity. In this study, Wistar rats were exposed to microwaves (30 mW/cm2 for 6 min, 3 times/week for 6 weeks). Spatial learning and memory function, distribution of dendritic spines, ultrastructure of the neurons and their dendritic spines in hippocampus as well as the related critical molecules of SNK-SPAR pathway were examined at different time points after microwave exposure. There was deficiency in spatial learning and memory in rats, loss of spines in granule cells and shrinkage of mature spines in pyramidal cells, accompanied with alteration of ultrastructure of hippocampus neurons. After exposure to 30 mW/cm2 microwave radiation, the up-regulated SNK induced decrease of SPAR and PSD-95, which was thought to cause the changes mentioned above. In conclusion, the microwave radiation led to shrinkage and even loss of dendritic spines in hippocampus by SNK-SPAR pathway, resulting in the cognitive impairments.

Biological effects and mechanisms of shortwave radiation: a review.

With the increasing knowledge of shortwave radiation, it is widely used in wireless communications, radar observations, industrial manufacturing, and medical treatments. Despite of the benefits from shortwave, these wide applications expose humans to the risk of shortwave electromagnetic radiation, which is alleged to cause potential damage to biological systems. This review focused on the exposure to shortwave electromagnetic radiation, considering in vitro, in vivo and epidemiological results that have provided insight into the biological effects and mechanisms of shortwave. Additionally, some protective measures and suggestions are discussed here in the hope of obtaining more benefits from shortwave with fewer health risks.

Microwave-induced Apoptosis and Cytotoxicity of NK Cells through ERK1/2 Signaling.

OBJECTIVE: To investigate microwave-induced morphological and functional injury of natural killer (NK) cells and uncover their mechanisms. METHODS: NK-92 cells were exposed to 10, 30, and 50 mW/cm2 microwaves for 5 min. Ultrastructural changes, cellular apoptosis and cell cycle regulation were detected at 1 h and 24 h after exposure. Cytotoxic activity was assayed at 1 h after exposure, while perforin and NKG2D expression were detected at 1 h, 6 h, and 12 h after exposure. To clarify the mechanisms, phosphorylated ERK (p-ERK) was detected at 1 h after exposure. Moreover, microwave-induced cellular apoptosis and cell cycle regulation were analyzed after blockade of ERK signaling by using U0126. RESULTS: Microwave-induced morphological and ultrastructural injury, dose-dependent apoptosis (P < 0.001) and cell cycle arrest (P < 0.001) were detected at 1 h after microwave exposure. Moreover, significant apoptosis was still detected at 24 h after 50 mW/cm2 microwave exposure (P < 0.01). In the 30 mW/cm2 microwave exposure model, microwaves impaired the cytotoxic activity of NK-92 cells at 1 h and down regulated perforin protein both at 1 h and 6 h after exposure (P < 0.05). Furthermore, p-ERK was down regulated at 1 h after exposure (P < 0.05), while ERK blockade significantly promoted microwave-induced apoptosis (P < 0.05) and downregulation of perforin (P < 0.01). CONCLUSION: Microwave dose-dependently induced morphological and functional injury in NK-92 cells, possibly through ERK-mediated regulation of apoptosis and perforin expression.