Brain inflammation is a marker of multiple sclerosis, Alzheimer's, and some psychiatric disorders. A new study finds a subtype of brain cell that is key in neuroinflammation, bringing us closer to new treatments for multiple central nervous system diseases.
Recent estimates suggest that 1 million people in the United States live with the condition.
However, neuroinflammation does not only characterize MS; recent studies show that depression, schizophrenia, and bipolar disorder are also linked to dysfunctions in the immune response, in addition to neurodegenerative disorders such as Alzheimer's.
Now, new research has furthered our understanding of this inflammatory process. Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) in San Diego, CA, have found that a subtype of astrocytes — that is, star-shaped, non-neuronal brain cells that support the good functioning of neurons — play a key role in the early onset of brain inflammation.
Dr. Jerold Chun, the senior vice president of Neuroscience Drug Discovery at SBP, led the research, which was just published in the journal eNeuro.
The role of 'ieAstrocytes' in an MS model
Dr. Chun and colleagues created a mouse model of MS, a condition they think "epitomizes" brain inflammation.
Using a fluorescent neuroimaging technique called cFos imaging, the scientists were able to see which nerve cells became activated, or "lit up," as the disease advanced.
Dr. Chun summarizes the team's findings, saying, "We expected to see immune cells light up — but surprisingly, they weren't activated. Neither were neurons or microglia."
Instead, they found that a subtype of astrocytes were activated early on, which the scientists called "immediate early astrocytes," or ieAstrocytes.
"ieAstrocytes," he says, "were the first and predominant cells activated during disease initiation and progression, suggesting that they are a key gatekeeper and mediator of disease."
He adds, "This is a departure from our previous understanding that astrocytes are spectator cells, only 'moving to the dark side' once initial damage has occurred."
Also, the number of ieAstrocytes increased as brain inflammation advanced and the disease got more severe. Furthermore, treating the mice with an MS drug called fingolimod reduced the number of these brain cells.
Better treatments for brain inflammation
"Greater understanding of ieAstrocytes could unlock more of the brain's mysteries," says Dr. Chun. "Defining these cells through their in vivo activity is an important first step, as it can help to guide therapeutic development using a readout that tracks with a brain disease."
"There is an urgent need," he goes on, "for treatments of brain inflammation disorders that are involved in many diseases, including MS and Alzheimer's disease."
"Developing therapies that prevent the formation of ieAstrocytes or reduce their activation levels in the brain could offer new approaches for treating neuroinflammatory and neurodegenerative diseases."
Dr. Jerold Chun