Since 2016, a team of MIT neuroscientists has been exploring the strange hypothesis that external exposure to a light flickering at 40 Hz can improve cognitive function and reverse the neurodegeneration associated with Alzheimer's disease. A new study has now homed in on exactly how, on a cellular level, this light treatment could be working.
Li-Huei Tsai and colleagues at MIT's Picower Institute for Learning and Memory first discovered in 2016 that amyloid and tau proteins seemed to be eliminated from mouse brains following exposure to a flickering light. Further work revealed adding a 40 Hz auditory tone to the process improved the efficacy of this treatment, however, it was not known exactly how this external stimuli was actually influencing the brain.
The new study set out to uncover exactly how a flickering light could stifle cognitive decline, using two unique mouse models engineered to overproduced the toxic proteins that contribute to neurodegeneration. The animals were exposed to light flickering at 40 Hz for one hour every day for between three and six weeks.
Incredibly, the mice engineered to overproduce tau proteins displayed no neuronal degeneration after three weeks of treatment compared to a control group that displayed nearly 20 percent total neuronal loss. The other mouse model, engineered to produce a neurodegenerative protein called p25, displayed no neurodegeneration whatsoever during the entire six weeks of treatment.
"I have been working with p25 protein for over 20 years, and I know this is a very neurotoxic protein," explains Tsai. "We found that the p25 transgene expression levels are exactly the same in treated and untreated mice, but there is no neurodegeneration in the treated mice. I haven't seen anything like that. It's very shocking."
The researchers then zoomed in on the light-treated animal's neurons and microglia to study whether the treatment induced any unusual changes in gene expression. The light-treated mice revealed increased neuronal expression of genes associated with synaptic function and DNA repair. In microglia, the brain's immune cells, there was a decrease in genes associated with inflammation.
All of this suggests that the flickering light treatment seems to induce brain activity that both enhances the ability of microglia to fight off inflammation and enables neurons to better protect and repair against damaging toxic proteins. Of course, these hypotheses still only offer a partial answer to the question of how this strange treatment is working.
The researchers now know what may be occurring in the brain to cause these beneficial results but, still, no one knows exactly how a 40 Hz flickering light can trigger these specific changes to gene expression deep in the brain. Further work in animal models is underway to better understand this unusual mechanism, while human trials testing the sound and light treatment in Alzheimer's patients have already begun.
The new study was published in the journal Neuron.
