Previous experiments using flickering light to treat neurodegenerative disease have shown promise, and now, researchers at the Georgia Institute of Technology (Georgia Tech) may have discovered how the flicker works. They found that exposure to light pulsing at 40 hertz (Hz) — 40 beats per second — caused the brains of healthy mice to release a surge of signaling chemicals that could help fight Alzheimer’s disease.
Though conducted on mice, the new study is connected to human trials, in which Alzheimer’s patients are exposed to 40 Hz light and sound. Insights gained by the Georgia Tech team are informing the human trials in collaboration with Emory University. Prior work has shown that exposing mice to lights flickering at 40 Hz induces neural spiking activity and recruits microglia, the primary immune cells of the brain. The microglia purge amyloid beta plaque, the junk protein that accumulates between the brain cells of Alzheimer’s patients. Researcher Annabelle Singer models an experimental visor and earphones that play 40-hertz light and sound. The current study was performed on mice. The pictured device is in human testing as a possible Alzheimer’s treatment. Results from those tests are to be published in later studies separate from the current study in mice. Courtesy of Georgia Tech/Allison Carter. However, the immediate effect of 40-Hz flicker on neuroimmune biochemical signaling was unknown. The new study looked for the brain chemistry that connects the flicker with microglial and other immune activation in mice. The researchers found that 40-Hz flicker led to a surge in the expression of cytokines, key immune signals known to recruit microglia. They further found that 40-Hz flicker rapidly changed the phosphorylation of proteins in two pathways known to regulate cytokine expression. The findings indicate that there is a specific rapid immune signaling response following 40-Hz visual stimulation and suggest that this form of treatment has therapeutic potential. The 40-Hz stimulation did not need long to trigger the cytokine surge. “We found an increase in cytokines after an hour of stimulation,” researcher Kristie Garza said. “We saw phosphoprotein signals after about 15 minutes of flickering.” “The phosphoproteins showed up first. It looked as though they were leading, and our hypothesis is that they triggered the release of the cytokines,” said professor Annabelle Singer, who co-led the study. A flickering light strip used to expose mice to 40-hertz light stimuli in Annabelle Singer’s lab. The exposure triggered strong releases of signaling chemicals in the brain. Courtesy of Georgia Tech/Allison Carter. As controls, the researchers applied three additional light stimuli. All three had an effect on cytokines, with 20 Hz having the greatest effect. “At 20 Hz, cytokine levels were way down. That could be useful, too. There may be circumstances where you want to suppress cytokines,” Singer said. “We’re thinking different kinds of stimulation could potentially become a platform of tools in a variety of contexts like Parkinson’s or schizophrenia. Many neurological disorders are associated with immune response.” The researchers will look for a causal connection to microglia activation in an upcoming study, but the overall surge of cytokines was a good sign in general, they said. They advise people not to improvise light therapies on their own, since more data is needed to thoroughly establish effects on humans, and getting frequencies wrong could possibly do damage. The research was published in the Journal of Neuroscience (www.doi.org/10.1523/JNEUROSCI.1511-19.2019). The hope of flickering light to treat Alzheimer’s takes a step forward in this study, which reveals that 40-hertz stimulation triggers a marked release of signaling chemicals. Courtesy of Georgia Tech/Evans/Karcz.