Mechanistic insights into microwave radiation induced cognitive impairments: The role of mA epigenetic modifications and HNRNPA2B1 in TrkB regulation

Microwave radiation, a prevalent environmental stressor, significantly impacts human health. Based on previous studies, we hypothesize that microwave-induced cognitive impairments and vulnerability in the hippocampal dentate gyrus (DG) region are due to abnormal synaptic plasticity regulated by both newborn and mature neurons derived from neural stem cells (NSCs). Epigenetics links external factors to organisms, offers insights into the health effects of environmental influences. To explore the molecular mechanisms underlying the effects of microwave radiation on neuronal synaptic plasticity from the perspective of mRNA N 6 -methyladenosine ( m 6 A ) modification. We first assessed the impact of microwave radiation on cognitive memory abilities in rats through behavioral tests. Immunofluorescence staining were applied to clarify the influence of microwave radiation on both neurons and NSCs. Molecular mechanisms were investigated by ELISA , q-PCR , Western blot , MeRIP-seq, and RNA pull-down experiments. The microwave radiated rat model exhibiting learning and memory deficits. Impaired synaptic plasticity in mature hippocampal neurons alongside hindered NSCs proliferation and development were observed. Using our established non-contact co-culture model, we replicated the in vivo adverse effects of microwave radiation. Down-regulated HNRNPA2B1 leads to reduced binding of TrkB m 6 A and promoted TrkB degradation. This feedback loop results in low BDNF expression, ultimately causing cognitive impairments. Our study emphasizes the neurotoxicity of microwave radiation and identifies TrkB m 6 A modification as a potential target for protecting against cognitive damage induced by electromagnetic radiation. Upon exposure to microwave radiation, both HNRNPA2B1 and TrkB m 6 A modifications levels decreased, leading to a subsequent reduction in TrkB expression. Within NSCs, this reduction in TrkB expression results in decreased uptake of BDNF, which impairs cellular proliferation and differentiation processes. Furthermore, within the synaptic structures of neurons, a feed-forward loop mechanism ensues, causing decreased BDNF secretion. This, in turn, inhibits dendritic growth in mature neurons and leads to aberrant synaptic plasticity. Collectively, the combined effects of these cellular alterations contribute to the observed cognitive impairments in rats following microwave radiation exposure. • Novel epi-transcriptomic mechanisms of microwave related neurocognitive risks were revealed. • Microwave radiation disrupts hippocampal synaptic plasticity and NSC development. • Microwave radiation down-regulates HNRNPA2B1, disrupts TrkB mRNA and BDNF expression. • TrkB m 6 A was a potential therapeutic target for microwave radiated cognitive damage.