Malicious brain cell identified

September 13, 2018

Astrocytes--the star-shaped cells of our brain--are very busy. Their job description includes maintaining the blood-brain barrier, removing excess neurotransmitters, repairing brain tissue and more.

Their important role in brain function suggests astrocytes are also involved in disease. Scientists are particularly interested in uncovering how they may drive inflammation in the brain. Brain inflammation is linked to a host of mysterious and devastating diseases, including multiple sclerosis (MS), Alzheimer's disease and mental illness. New treatments are urgently needed for these disorders.

Now, scientists at Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified an astrocyte subpopulation as the dominant cell type to spring into action in vivo (in a living organism) in a neuroinflammatory disease setting. Their early activation inspired their new name: ieAstrocytes (immediate early astrocytes). The study published today in eNeuro.

"There is an urgent need for treatments of brain inflammation disorders that are involved in many diseases, including MS and Alzheimer's disease," says Jerold Chun, M.D., Ph.D., senior author of the paper and professor and senior vice president of Neuroscience Drug Discovery at SBP. "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."

The scientists identified the new type of astrocyte using an unbiased, fluorescent labeling technique to visualize the most active brain cells that express an activity-dependent transcription factor, cFos. Cells that were "turned on" glowed green, allowing the researchers to track activated cells over time and space. Applying this method to a mouse model of brain inflammation allowed visualization of which cells were activated as the disease progressed.

"We expected to see immune cells light up--but surprisingly, they weren't activated. Neither were neurons or microglia," says Chun. "ieAstrocytes were the first and predominant cells activated during disease initiation and progression, suggesting that they are a key gatekeeper and mediator of disease. This is a departure from our previous understanding that astrocytes are spectator cells, only 'moving to the dark side' once initial damage has occurred."

ieAstrocytes increased in number as brain inflammation progressed, indicating they play a key role in disease. Treating the brain cells in an in vivo experiment with a U.S. Food and Drug Administration (FDA)-approved drug for MS, GILENYA® (fingolimod), reduced ieAstrocyte formation, further implicating their role in disease and identifying direct brain effects of the drug.

"Greater understanding of ieAstroycytes could unlock more of the brain's mysteries," says 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."

Chun's team is already working on their next step: characterizing these astrocytes at the molecular level, particularly the specific genes that are activated.
-end-
Co-first authors of the study are Aran Groves, M.D., Ph.D., now a resident pediatric physician at UCLA; Yasuyuki Kihara, Ph.D., research assistant professor at SBP; and Deepa Jonnalagadda, Ph.D., postdoctoral associate at SBP. Additional co-authors include: Richard Rivera and Grace Kennedy, SBP; and Mark Mayford, UC San Diego. The study's DOI is 10.1523/ENEURO.0239-18.2018.

Research reported in this press release was supported by a grant from Novartis; National Institutes of Health (NIH) grants NS084398, DA019674 and R01NS10394; and fellowship support from the Uehara Memorial Foundation, the Kanae Foundation for the Promotion of Medical Science, Mochida Memorial Foundation for Medical and Pharmaceutical Research, and the Human Frontier Science Program. Groves was supported by the Medical Scientist Training Program and Pharmacology Training Grant at the University of California, San Diego (T32GM007752). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

About Sanford Burnham Prebys Medical Discovery Institute

Sanford Burnham Prebys Medical Discovery Institute (SBP) is an independent nonprofit medical research organization that conducts world-class, collaborative, biological research and translates its discoveries for the benefit of patients. SBP focuses its research on cancer, immunity, neurodegeneration, metabolic disorders and rare children's diseases. The Institute invests in talent, technology and partnerships to accelerate the translation of laboratory discoveries that will have the greatest impact on patients. Recognized for its NCI-designated Cancer Center and the Conrad Prebys Center for Chemical Genomics, SBP employs nearly 900 scientists and staff in San Diego (La Jolla), Calif., and Orlando (Lake Nona), Fla. For more information, visit us at SBPdiscovery.org or on Facebook at facebook.com/SBPdiscovery and on Twitter @SBPdiscovery.

Sanford Burnham Prebys Medical Discovery Institute

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.