Far Infrared Light Irradiation Enhances Microglial Aβ Clearance and Ameliorates Cognitive Deficit in Alzheimer’s Disease-like Mice

Abstract Background: Exposure to sunlight may decrease the risk of developing Alzheimer’s disease (AD). However, the wavelength of the light with this therapeutic effect and the related mechanism remain elusive. Failure to clear amyloid-β (Aβ), the main component of amyloid plaque, has been considered as a key risk to cause the development of AD. As the resident immune cell in the brain, microglia is able to carry out Aβ clearance. We hypothesize that a component of sunlight improves AD-related cognitive dysfunction and that this beneficial effect may be via Aβ clearance by microglia. Method: The APP/PS1 mice by 8.5 months of age were exposed to the visible light (λ = 500 nm), near infrared light (λ = 800 nm) and far infrared light (λ = 3 - 25 µm) for 60 min per day. After 5-week treatment with different light, all mice began to be subjected to Morris water maze behavior test under SPF environment. Western blotting was carried out to detect the expression of postsynaptic density-95 protein and synaptophysin in the hippocampus. The protein amount of interleukin (IL)-1β and IL-6 in the cerebral cortex were determined by using ELISA kits. Immunostaining was performed to characterize the Aβ, microglia, cluster of differentiation 68. Under the condition of Aβ existing, primary cultured microglia were treated with light for 2 h before Aβ phagocytosis assay.Results: The APP/PS1 mice with different light (VIS, NIR and FIR) treatments showed a trend of improvement in learning compared to those without light treatment during training stage. Moreover, FIR light-treated APP/PS1 mice had better spatial memory than APP/PS1 mice in the probe test. Simultaneously, FIR light treatment restored synaptophysin protein expression, promoted the recruitment of microglia to Aβ plaques, enhanced the phagocytosis of Aβ, reduced Aβ burden and alleviated neuroinflammation.Conclusions: Taken together, FIR light treatment ameliorates the learning and memory impairment in AD-like mice. Our findings uncovered a previously unappreciated function of FIR light, suggesting that FIR light treatment may be a potential therapeutic strategy for AD.