Exosomes Derived from M2 Microglial Cells Modulated by 1070‐nm Light Improve Cognition in an Alzheimer's Disease Mouse Model

Abstract Near‐infrared photobiomodulation has been identified as a potential strategy for Alzheimer's disease (AD). However, the mechanisms underlying this therapeutic effect remain poorly characterize. Herein, it is illustrate that 1070‐nm light induces the morphological alteration of microglia from an M1 to M2 phenotype that secretes exosomes, which alleviates the β‐amyloid burden to improve cognitive function by ameliorating neuroinflammation and promoting neuronal dendritic spine plasticity. The results show that 4 J cm −2 1070‐nm light at a 10‐Hz frequency prompts microglia with an M1 inflammatory type to switch to an M2 anti‐inflammatory type. This induces secretion of M2 microglial‐derived exosomes containing miR‐7670‐3p, which targets activating transcription factor 6 (ATF6) during endoplasmic reticulum (ER) stress. Moreover, it is found that miR‐7670‐3p reduces ATF6 expression to further ameliorate ER stress, thus attenuating the inflammatory response and protecting dendritic spine integrity of neurons in the cortex and hippocampus of 5xFAD mice, ultimately leading to improvements in cognitive function. This study highlights the critical role of exosomes derive from 1070‐nm light‐modulated microglia in treating AD mice, which may provide a theoretical basis for the treatment of AD with the use of near‐infrared photobiomodulation.