Microwave radiation induces neuronal autophagy through miR-30a-5p/AMPKα2 signal pathway

Abstract

The potential health hazards of microwaves have attracted much more attention. Our previous study found that 2856 MHz microwave radiation damaged synaptic plasticity and activated autophagy in neurons. However, the mechanisms underlying microwave induced autophagy were still unclear. In the present study, we established neuronal damage models by exposing rat hippocampal neurons and rat adrenal pheochromocytoma (PC12) cell-derived neuron-like cells to 30 mW/cm2 microwaves, which resulted in miR-30a-5p (“miR-30a” for short) downregulation and autophagy activation in vivo and in vitro. Bioinformatics analysis was conducted, and Beclin1, Prkaa2, Irs1, Pik3r2, Rras2, Ddit4, Gabarapl2 and autophagy-related gene 12 (Atg12) were identified as potential downstream genes of miR-30a involved in regulating autophagy. Based on our previous findings that microwave radiation could lead to abnormal energy metabolism in neurons, Prkaa2, encoding adenosine 5’-monophosphate-activated protein kinase α2 (AMPKα2, an important catalytic subunit of energy sensor AMPK), was selected for further analysis. Dual-luciferase reporter assay results showed that Prkaa2 was a downstream gene of miR-30a. Moreover, microwave radiation increased the expression of AMPKα2 and the phosphorylation of AMPKα (Thr172) both in vivo and in vitro. The transfection of PC12 cells with miR-30a mimics increased miR-30a levels, reduced AMPKα2 expression, suppressed AMPKα (Thr172) phosphorylation, and inhibited autophagy occurrence in neuron-like cells. Importantly, miR-30a overexpression abolished microwave-activated autophagy and inhibited microwave-induced AMPKα2 upregulation and AMPKα (Thr172) phosphorylation. In conclusion, AMPKα2 was a newly identified downstream genes of miR-30a, microwave radiation promoted the occurrence of autophagy in neurons through the miR-30a/AMPKα2 pathway.

Accumulative Effects of Multifrequency Microwave Exposure with 1.5 GHz and 2.8 GHz on the Structures and Functions of the Immune System

“…Our group previously established stable animal models to evaluate the nonthermal effects of microwaves ( Supplementary Figure S2 ), and the nonthermal effects on the hippocampus, heart, and testis were evaluated. Our data suggested that power-density-dependent injuries could be detected in these tissues [ 10 , 25 , 48 , 49 ]. In this study, we exposed rats to a multifrequency microwave of 1.5 GHz and 2.8 GHz, the body temperature was monitored both before and immediately after exposure, and no obvious changes were observed.…”

Calcium Imaging Characterize the Neurobiological Effect of Terahertz Radiation in Zebrafish Larvae

“…However, there are few studies on microwave irradiation’s positive regulation of neuronal activity. Studies have found that microwave radiation damages the synaptic plasticity of neurons and activates neuron autophagy, thereby impairing learning and memory [ 43 , 44 , 45 , 46 ]. In summary, mid-infrared or THz waves with the appropriate frequency and intensity can enhance neuronal function.…”

Microwave Radiation and the Brain: Mechanisms, Current Status, and Future Prospects

“…The CNS was determined to be the most vulnerable to microwave radiations [ 68 ], with the hippocampus being particularly sensitive [ 69 , 70 , 71 , 72 ]. Specifically, microwaves can damage the brain (one of the two key components of the human CNS), particularly affecting the neurotransmitters which play an important role in passing signals inside the body [ 73 ].…”

“…Notably, these findings offer insight into observing the combined effects of different frequencies that are commonly present in the atmosphere. Elsewhere, recent in vivo and in vitro studies have reported that microwave radiation causes autophagy in neuronal cells by activating the miR-30a/AMPKα2 pathway [ 71 ]. Furthermore, evidence supports the presence of nonthermal effects and exposure difficulties for the blood barrier of the brain [ 114 ], with 1.5 and 2.856 GHz microwave radiation exposure inducing a decline in spatial memory [ 115 ].…”