Near-Infrared Light Reduces Glia Activation and Modulates Neuroinflammation in Brain of Diet-Induced Obese Mice

Obesity is one of the most prominent risk factors for Alzheimer’s Disease (AD); obesity and AD share several pathological features, in particular the neuroinflammation. Hippocampal neuroinflammation, in rodents, correlates with poor memory performance, while in humans, growing evidence shows that obesity increases three times the risk of developing AD. The overall objective of this work is to reduce the impact of obesity on neuroinflammation, that in turn may lead to dementia. In last years, near-infrared (NIR) light has been proposed as potential treatment, showing improvement of learning and memory in both humans and animal models. Previous work demonstrated that a transcranial delivery of NIR light reduced Aβ and Tau pathology and improved memory function in mouse models of AD. Here, it was tested whether NIR light may prevent obesity-induced neuroinflammation, in a diet-induced obese mouse model of obesity. After 13 weeks of high-fat diet (HFD), the mice received the NIR light treatments for 4 weeks in single daily sessions of 90 seconds each. The immunostaining investigations performed on brain slices to evaluate glial activation revealed that in both hippocampus and parietal/occipital cortex, HFD caused increased expression of CD68 (activated microglia) and GFAP (astrocytic marker), whereas NIR light reverses this increase. On the other hand, the same investigations displayed no change in frontal cortex. Furthermore, I evaluated the effects of light on cytokines in hippocampus and frontal cortex, by using quantitative real-time PCR analyses: in the hippocampus, HFD caused the increase of pro-inflammatory IL-1β and TNF-α, as well as of the anti-inflammatory IL-10, while NIR light lowers their levels. Also, BDNF resulted upregulated in HFD mice treated with NIR light, compared to HFD not-treated mice, thus suggesting that the NIR light triggers neuroprotective effects resulting in reduced neuroinflammation. Interestingly, the levels of cytokines and BDNF were unchanged in the frontal cortex. Collectively, this data suggests that neuroinflammation is reduced by NIR light and it is a reversible process that may be targeted to prevent neurodegeneration. Moreover, NIR light poses as a potential preventive and non-invasive therapeutic approach against obesity-induced CNS deficits that are known to concur to AD neuropathological cascade.