Researchers at Massachusetts General Hospital have used a new sequencing method to pinpoint a group of genes known as microglia–immune cells in the brain, to locate any pathogenic organisms, toxins or damaged cells in their environment. This ‘microglial sensome’ could lead to a more thorough understanding of the role microglia plays in both normal brains and in neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Microglia constantly examine their environment to detect the presence of any infection, inflammation and injured or dying cells. If there is a threat to their environment, microglia react in a defensive manner and release toxic substances to engulf and destroy microbes or infected brain cells.
Joseph El Khoury, MD, of the MGH Center for Immunology and Inflammatory Diseases and Division of Infectious Diseases decided to define the complete set of RNA molecules transcribed by the cells in the microglia of healthy, adult mice and compared it to those of macrophages from peripheral tissues in adult mice. Using RNA sequencing, Dr. Khoury and associates were able to identify a set of genes unique to the microglia and measure the genes expression levels.
Previous studies had indicated that aging alters gene expression throughout the brain, so Dr. Khoury decided to compare the microglial sensome of young adult mice to that of aged mice. Contrary to previous studies, they found the activity of microglia to be more protective with aging as opposed to increasingly toxic. Dr. Khoury believes previous studies did not look at the cells’ entire expression profile and were more often done in cultured cells rather than living animals.
Now that researchers understand how the microglia sensome interacts and responds to their environment, the next step is to study what happens under pathologic conditions. It is understood that microglia become more neurotoxic as Alzheimer’s and other neurodegenerative diseases progress, however until researchers identify exactly how the microglia sensome changes during central nervous system disorders, they will be one step further from finding a drug to combat these disorders.
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