Far infrared light irradiation enhances Aβ clearance via increased exocytotic microglial ATP and ameliorates cognitive deficit in Alzheimer's disease-like mice

Background: Exposure to sunlight may decrease the risk of developing Alzheimer's disease (AD), and visible and near infrared light have been proposed as a possible therapeutic strategy for AD. Here, we investigated the effects of the visible, near infrared and far infrared (FIR) light on the cognitive ability of AD mice, and found that FIR light also showed potential in the improvement of cognitive dysfunction in AD. However, the related mechanism remains to be elucidated. Methods: Morris water maze was used to evaluate the cognitive ability of APPswe/PSEN1dE9 double-transgenic AD mice after light treatment. Western blot was carried out to detect the expression of protein involved in synaptic function and amyloid-beta (A beta) production. The protein amount of interleukin (IL)-1 beta, IL-6, A beta(1-40) and A beta(1-42) were determined using enzyme-linked immunosorbent assay. The mRNA level of receptors was performed using real-time quantitative polymerase chain reaction. Immunostaining was performed to characterize the A beta burden and microglial A beta phagocytosis in the brain of AD mice. The A beta phagocytosis of primary cultured microglia and BV2 were assessed by flow cytometry. The energy metabolism changes were evaluated using related assay kits, including adenosine triphosphate (ATP), lactate content, mitochondrial respiratory chain complex enzymatic activity and oxidized/reduced nicotinamide adenine dinucleotide assay kits. Results: Our results showed that FIR light reduced A beta burden, a hallmark of AD neuropathology, alleviated neuroinflammation, restored the expression of the presynaptic protein synaptophysin, and ameliorated learning and memory impairment in the AD mice. FIR light enhanced mitochondrial oxidative phosphorylation pathway to increase ATP production. This increased intracellular ATP promoted the extracellular ATP release from microglia stimulated by A beta, leading to the enhanced A beta phagocytosis through phosphoinositide 3-kinase/mammalian target of rapamycin pathways for A beta clearance. Conclusions: Our findings have uncovered a previously unappreciated function of FIR light in inducing microglial phagocytosis to clean A beta, which may be the mechanisms for FIR light to improve cognitive dysfunction in AD mice. These results suggest that FIR light treatment is a potential therapeutic strategy for AD.

Automated summary

This study found that far infrared (FIR) light can reduce A beta burden, alleviate neuroinflammation, and improve learning and memory impairment in AD mice. FIR light enhances mitochondrial oxidative phosphorylation pathway to increase ATP production, thereby enhancing the phagocytosis and clearance of A beta. These findings suggest that FIR light treatment may be a potential therapeutic strategy for AD.