Exosomes Derived from M2 Microglial Cells Modulated by 1070-nm Light Improve Cognition in an Alzheimer's Disease Mouse Model
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Published on: March 16, 2016
Chengwei Chen1,2,3,4,5, Yuting Bao1,2,3,4,5, Lu Xing1,2,3,4,5
1Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China.
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.
Insights
Near-infrared photobiomodulation therapy shifts microglia to an anti-inflammatory state, releasing exosomes that reduce Alzheimer's disease pathology and improve cognitive function in mice.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Cell Biology
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta plaques and neuroinflammation.
- Near-infrared photobiomodulation (NIR-PBM) shows promise for AD treatment, but its underlying mechanisms require elucidation.
- Microglia play a crucial role in AD pathogenesis, with their phenotypes (M1/M2) influencing disease progression.
Purpose of the Study:
- To investigate the molecular mechanisms by which 1070-nm light photobiomodulation impacts microglia and affects Alzheimer's disease pathology.
- To determine if NIR-PBM can modulate microglial phenotype and influence exosome secretion for therapeutic benefit in AD models.
Main Methods:
- Utilized 5xFAD mouse model of Alzheimer's disease.
- Applied 1070-nm light photobiomodulation at 4 J/cm² and 10 Hz frequency.
- Analyzed microglial morphology and phenotype (M1/M2 markers).
- Quantified exosome secretion and characterized their miRNA content (miR-7670-3p).
- Assessed the impact on endoplasmic reticulum (ER) stress, neuronal dendritic spine plasticity, and cognitive function.
Main Results:
- 1070-nm light induced a phenotypic switch of microglia from M1 (inflammatory) to M2 (anti-inflammatory) state.
- M2 microglia secreted exosomes enriched with miR-7670-3p.
- miR-7670-3p targeted and reduced activating transcription factor 6 (ATF6) expression, alleviating ER stress.
- Treatment attenuated neuroinflammation, protected neuronal dendritic spine integrity in the cortex and hippocampus, and improved cognitive function in 5xFAD mice.
Conclusions:
- NIR-PBM effectively modulates microglia phenotype, promoting an anti-inflammatory M2 state.
- Exosomes derived from NIR-PBM-treated M2 microglia carry therapeutic potential via miR-7670-3p.
- This exosome-mediated mechanism ameliorates ER stress, reduces neuroinflammation, and restores neuronal plasticity, offering a novel therapeutic strategy for Alzheimer's disease.
