Microglia’s dual role: policeman, electrician
By Jack Mazurak
New findings in often overlooked brain cells called microglia could lead to better understanding of – and possibly treatments for – neurological disorders, including autism, ALS, multiple sclerosis and Parkinson’s disease.
Research by two University of Mississippi Medical Center neuroscientists investigated the apparent dual role of microglia: one as a policeman, the other as an electrician.
“We’re learning more about the role microglia play in forming myelin around the brain tracts during development,” said Dr. Rick Lin, professor of neurobiology and anatomical sciences.
Myelin is a fatty coating that essentially insulates the wires of the brain’s electrical circuitry.
“The clinical implications of knowing more about that process – and maybe controlling it – are enormous because so many neurologic diseases result in myelin dysfunction,” said Lin, who also holds faculty appointments in the Departments of Pediatrics and Psychiatry.
In their police role, microglia serve as part of the body’s immune system, protecting the brain from invading pathogens. They also respond to trauma sites, possibly to hold down swelling.
The new research projects from the labs of Lin and Dr. Yi Pang, assistant professor of pediatrics, indicate microglia cells are electricians involved with myelination during brain development.
Pang used a drug to eliminate microglia in the brains of developing rats. When the rats grew to the equivalent of early childhood, he analyzed each brain.
“We found that anywhere we’d injected the drug in the white matter there were no microglia and reduced – or even no – myelination,” Pang said.
His experiment used only four treated and three control rats, so he plans to repeat it with more to produce statistically relevant data.
“These are preliminary data only. But they indicate there is a link between microglia and myelination,” he said.
Pang’s lab has published findings in cell culture that link microglia to the myelin-production process. But this poster is the first to test the hypothesis in animals.
Lin’s project relied on microglia’s snap transformation from their resting,
compact shape into an activated form with spindles extended, allowing them to engulf intruders.
His team treated more than 20 rat pups daily with therapeutic-level doses of the antidepressant Citalopram, beginning at eight days old through two weeks. That time period of rat brain development corresponds to the final trimester in human pregnancy and first few years of life.
Such early exposure produces rats that exhibit key behaviors, deficiencies and brain malformations seen in autism, including myelination problems.
Lin and his autism research team let the rats reach adulthood – between six and eight months – then examined their brains. Each of the 20-plus treated rats had activated microglia.
This novel finding points toward a possible connection between the immune system job of activated microglia and their role in support of myelination during brain development.
Lin and Pang each discussed their research at the Society for Neuroscience meeting Nov. 10 in San Diego. Andrew Gargiulo, an undergraduate senior and neuroscience major at Millsaps College, presented Lin’s poster.
In the future, Lin and Pang plan to investigate the “where” and “when” questions, since microglia activation can be harmful or beneficial in different brain regions during different developmental stages.
“These basic mechanisms are very important for understanding disease processes,” Lin said.
Pang said such insight could guide drug development for diseases like multiple sclerosis.