Assessing effects of microwave electromagnetic field in APP/PS1 mice by in vivo GABA-weighted imaging via variable delay multipulse-chemical exchange saturation transfer MRI

Abstract

Electromagnetic fields (EMFs) have been shown to be beneficial in treating Alzheimer's disease (AD), but the underlying neurophysiological mechanisms remain unclear. It has been proposed that EMF promotes GABAergic neurogenesis and that abnormal GABA levels are an important influence on the progression of AD. To achieve in vivo GABA-weighted imaging in the brain in APP/PS1 mice, we utilized variable delay multi-pulse (VDMP)-chemical exchange saturation transfer (CEST)- magnetic resonance imaging (MRI) and pathological validation to measure GABA levels in APP/PS1 mice under microwave EMF and explore the therapeutic mechanism. The APP/PS1 mice received a 4-week microwave EMF treatment. The findings show that microwave EMF stimulation significantly increased GABA-weighted signals on MRI of APP/PS1 mouse hippocampus. VDMP-CEST was sensitive in detecting GABA-weighted signals. ELISA showed that microwave EMF stimulation elevated GABA levels in the hippocampus. Compared to in vitro levels, VDMP-CEST accurately detected GABA-weighted signal changes. With the pathological validations, we found that microwave EMF exposure can elevate hippocampal GABA levels by promoting AQP4 polarizion, reducing Aβ accumulation and neuronal degeneration, improving cognitive impairment, and may have slowed AD progression. Collectively, microwave EMF treatment could increase GABA-related changes, which corresponded to the accumulation of Aβ and improvement in the water maze. VDMP-CEST detected levels are highly consistent with pathological evidence, implying that VDMP-CEST is an effective modality for in vivo GABA-weighted imaging during microwave EMF treatment, providing more objective imaging-based diagnostic evidence for monitoring GABA-related pathological changes in AD.