Colgate University Researchers Publish on Early Immune Response to Brain White Matter Disease

New research from Colgate University Assistant Professor of Psychological and Brain Sciences and Neuroscience Anzela Niraula, Ashley Shanahan '27, and Gwen Eichfeld '25 sheds light on the changing nature of the brain's immune response to neurodegenerative, demyelinating diseases, like multiple sclerosis.

Our ability to talk, walk, and react to stimuli in the environment depends on electrical signals traveling between neurons in the brain. Those neurons are insulated by myelin, layers of fat and proteins that prevent signals from straying off and disrupting communication within the brain. Diseases like multiple sclerosis destroy the fatty insulation on neurons, creating a mess in the brain and preventing signals from reaching their destination.

"Anytime there is damage, immune cells called microglia that live in the brain will respond," Niraula says. "These cells turn on the genes that they would need to try to eat the debris."

Previous studies, which focus only on the long-term impact of the disease, have established that microglia are not efficient at clearing away damage at five weeks into disease progression. Instead, they produce reactive oxygen species and signals that promote inflammation.

"If other cells are sprayed with that, they could die," Niraula says. "Neurons or other cells that are supposed to be producing new myelin could be killed or impaired by these immune cells."

Since 2024, Niraula and her student-researchers have been asking, "Do microglia go from completely helpful at one point to harmful at another point? Or are they always producing inflammatory signals?"

The team's paper, published this week in PLOS One, looks closely at the first week of disease in animal models. Their findings show that, at this early phase, when the myelin is being destroyed, the immune cells activate and rush in only as anticipated - absorbing damaged myelin without producing inflammatory signals. "At this early time point, we did not see evidence of damaging signals being produced in the brain - these cells harming other cells. They are helping in an adaptive, constructive way."

Based on these results, the team now knows that a switch happens somewhere between one and five weeks of disease. This is an important fact to establish, because it could have implications for the treatment of MS and other neurodegenerative diseases in humans - allowing physicians to use immune cells to early advantage and then silence them when they become harmful.

Work on the project began in 2024 as part of Eichfeld's honors thesis and now includes collaboration with researchers at SUNY Upstate. Investigation of immune response to myelin damage continues in Niraula's lab as she and her students study the impact of pharmaceutical interventions on immune cells, whether they promote or hinder the ability of the cells to clear myelin debris.