Nav: Home

Discovery may advance neural stem cell treatments for brain disorders

January 24, 2018

La Jolla, Calif., January 24, 2017 - New research from Sanford Burnham Prebys Medical Discovery Institute (SBP) is among the first to describe how an mRNA modification impacts the life of neural stem cells (NSCs). The study, published in Nature Neuroscience, reveals a novel gene regulatory system that may advance stem cell therapies and gene-targeting treatments for neurological diseases such as Alzheimer's disease, Parkinson's disease, and mental health disorders that affect cognitive abilities.

"Being able to maintain viable stem cells in the brain could lead to regenerative therapies to treat injury and disease," says Jing Crystal Zhao, Ph.D., assistant professor at SBP. "Our study reveals a previously unknown but essential function of an mRNA modification in regulating NSC self-renewal. As NSCs are increasingly explored as a cell replacement therapy for neurological disorders, understanding the basic biology of NSCs--including how they self-renew--is essential to harnessing control of their in vivo functions in the brain."

NSCs are progenitor cells present not only during embryonic development but also in the adult brain. NSCs undergo a self-renewal process to maintain their population, as well as differentiate to give rise to all neural cell types: neurons, astrocytes and oligodedrocytes.

The current study focused on the self-renewal aspect of NSCs. Using knockout mice (KO) for the enzyme that catalyzes the m6A modification, Zhao's team found that m6A modification maintains NSC pool by promoting proliferation and preventing premature differentiation of NSCs. Importantly, the researchers found that m6A modification regulates this by regulating histone modifications.

Histones--the proteins in cells that bind and package DNA--and their modifications play an important role in whether genes are turned "on" or "off". Some histone modifications compact the DNA to hide a gene from the cell's protein-making machinery and consequently turn gene "off". On the other hand, histone modifications can also loosen up DNA for gene exposure to turn gene "on".

"Our findings are the first to illustrate cross-talk between mRNA and histone modifications, and may lead to new ways to target genes in the brain," says Zhao.

"Conceptually, we could use the modification, which is the methylation of adenosine residues, as a 'code' in mRNA to target histone modifications to turn gene on or off," says Zhao.

Drugs that alter histones have a long history of use in psychiatry and neurology, and increasingly in cancer. But current drugs that modify histones are often times non-specific; they work across the entire genome.

"Our current study addressed the interaction between mRNA and histone modification in a genome-wide scale. In the future, we plan to study such interaction on a gene-by-gene basis. Ultimately, by modulating mRNA modification and its interacting histone modifications at a specific genomic region, we hope to correct aberrant gene expression in brain disorders with precision," explains Zhao.
-end-
Co-authors of the paper include: Yang Wang, Jun Wang, Sandeep Kumar, Robert Wechsler-Reya, Gregg Duester (SBP), Yue Li, Manolis Kellis (MIT), Minghui Yue, Yuya Ogawa (University of Cincinnati), and Zhaolei Zhang, (University of Toronto).

This study was funded by CIHR Operating Grant No. 115194, NSERC Discovery Grant 327612, NCI grant CA159859, CIRM Leadership Award LA1-01747, NIGMS grant GM062848, NIH RO1 award MH109978 and HG008155, NIH RF1 award AG054012, NIH U01 award HG007610, CIRM Training Grant TG2-0112, NIH R01 award GM110090 and an SBP Cancer Center Pilot grant 5P30 CA030199.

About SBP

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 world-class NCI-designated Cancer Center and the Conrad Prebys Center for Chemical Genomics, SBP employs about 975 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:

Study describes changes to structural brain networks after radiotherapy for brain tumors
Researchers compared the thickness of brain cortex in patients with brain tumors before and after radiation therapy was applied and found significant dose-dependent changes in the structural properties of cortical neural networks, at both the local and global level.
Blue Brain team discovers a multi-dimensional universe in brain networks
Using a sophisticated type of mathematics in a way that it has never been used before in neuroscience, a team from the Blue Brain Project has uncovered a universe of multi-dimensional geometrical structures and spaces within the networks of the brain.
New brain mapping tool produces higher resolution data during brain surgery
Researchers have developed a new device to map the brain during surgery and distinguish between healthy and diseased tissues.
Newborn baby brain scans will help scientists track brain development
Scientists have today published ground-breaking scans of newborn babies' brains which researchers from all over the world can download and use to study how the human brain develops.
New test may quickly identify mild traumatic brain injury with underlying brain damage
A new test using peripheral vision reaction time could lead to earlier diagnosis and more effective treatment of mild traumatic brain injury, often referred to as a concussion.
This is your brain on God: Spiritual experiences activate brain reward circuits
Religious and spiritual experiences activate the brain reward circuits in much the same way as love, sex, gambling, drugs and music, report researchers at the University of Utah School of Medicine.
Brain scientists at TU Dresden examine brain networks during short-term task learning
'Practice makes perfect' is a common saying. We all have experienced that the initially effortful implementation of novel tasks is becoming rapidly easier and more fluent after only a few repetitions.
Balancing time & space in the brain: New model holds promise for predicting brain dynamics
A team of scientists has extended the balanced network model to provide deep and testable predictions linking brain circuits to brain activity.
New view of brain development: Striking differences between adult and newborn mouse brain
Spikes in neuronal activity in young mice do not spur corresponding boosts in blood flow -- a discovery that stands in stark contrast to the adult mouse brain.
Map of teenage brain provides evidence of link between antisocial behavior and brain development
The brains of teenagers with serious antisocial behavior problems differ significantly in structure to those of their peers, providing the clearest evidence to date that their behavior stems from changes in brain development in early life, according to new research led by the University of Cambridge and the University of Southampton, in collaboration with the University of Rome Tor Vergata in Italy.

Related Brain Reading:

The Brain's Way of Healing: Remarkable Discoveries and Recoveries from the Frontiers of Neuroplasticity
by Norman Doidge (Author)

NEW YORK TIMES BESTSELLER

 The New York Times–bestselling author of The Brain That Changes Itself presents astounding advances in the treatment of brain injury and illness. Now in an updated and expanded paperback edition.

Winner of the 2015 Gold Nautilus Award in Science & Cosmology 

In his groundbreaking work The Brain That Changes Itself, Norman Doidge introduced readers to neuroplasticity—the brain’s ability to change its own structure and function in response to activity and mental experience. Now his revolutionary... View Details


The Brain: The Story of You
by David Eagleman (Author)

Locked in the silence and darkness of your skull, your brain fashions the rich narratives of your reality and your identity. Join renowned neuroscientist David Eagleman for a journey into the questions at the mysterious heart of our existence. What is reality? Who are “you”? How do you make decisions? Why does your brain need other people? How is technology poised to change what it means to be human?  In the course of his investigations, Eagleman guides us through the world of extreme sports, criminal justice, facial expressions, genocide, brain surgery, gut feelings, robotics, and the... View Details


Your Fantastic Elastic Brain: Stretch It, Shape It
by JoAnn Deak Ph.D. (Author), Sarah Ackerley (Illustrator)

A Mom's Choice Gold Award Winner!

What does your brain really do?

Did you know you can stretch and grown your own brain? Or that making mistakes is one of the best ways your brain learns? Just like how lifting weights helps your muscles get stronger, trying new things without giving up strengthens your brain.

This fun and engaging introduction to the anatomy and functions of the brain will empower each young reader to S-T-R-E-T-C-H and grow their Fantastic, Elastic Brain!

Other Awards for Your Fantastic,... View Details


Brain Maker: The Power of Gut Microbes to Heal and Protect Your Brain–for Life
by David Perlmutter (Author), Kristin Loberg (Contributor)

The bestselling author of Grain Brain uncovers the powerful role of gut bacteria in determining your brain's destiny.

Debilitating brain disorders are on the rise-from children diagnosed with autism and ADHD to adults developing dementia at younger ages than ever before. But a medical revolution is underway that can solve this problem: Astonishing new research is revealing that the health of your brain is, to an extraordinary degree, dictated by the state of your microbiome - the vast population of organisms that live in your body and outnumber your own cells... View Details


The Brain: All about Our Nervous System and More!
by Seymour Simon (Author)

Exceptional nonfiction for children from two of the most trusted names in science education: Seymour Simon and the Smithsonian Institution.

Book Details:Format: PaperbackPublication Date: 5/23/2006Pages: 32Reading Level: Age 6 and Up View Details


Switch On Your Brain: The Key to Peak Happiness, Thinking, and Health
by Dr. Caroline Leaf (Author)

Scientist and therapist helps readers understand how the power of their thoughts can help them manage stress, break unhealthy patterns, use their brains more effectively, and overcome mental, emotional, physical, and spiritual obstacles. View Details


Neuroscience: Exploring the Brain
by Mark F. Bear (Author), Barry W. Connors (Author), Michael A. Paradiso (Author)

Publisher’s Note:   Products purchased from 3rd Party sellers are not guaranteed by the Publisher for quality, authenticity, or access to any online entitlements included with the product.

Acclaimed for its clear, friendly style, excellent illustrations, leading author team, and compelling theme of exploration, Neuroscience: Exploring the Brain, 4e takes a fresh, contemporary approach to the study of neuroscience, emphasizing the biological basis of behavior. The authors’ passion for the dynamic field of neuroscience is evident on every page, engaging students... View Details


The Better Brain Solution: How to Start Now--at Any Age--to Reverse and Prevent Insulin Resistance of the Brain, Sharpen Cognitive Function, and Avoid Memory Loss
by Steven Masley (Author)

Diabetes ... Alzheimer's disease ... here, from the author of the best-selling 30-Day Heart Tune-Up and Smart Fat, is the first book to show how the brain can become insulin resistant through diet and lifestyle, and to make clear how and why this has been directly linked to cognitive decline and memory loss. With a detailed program developed by the author to prevent and reverse this potentially devastating condition.

Alzheimer's disease is the #1 most terrifying disease today. Despite billions of dollars of research, there are no significant cures for dementia or... View Details


Grain Brain: The Surprising Truth about Wheat, Carbs, and Sugar--Your Brain's Silent Killers
by David Perlmutter (Author), Kristin Loberg (Contributor)

New, unopened, unused hardcover with dust jacket, including at no extra cost a new unused copy of The Brain Grain Cookbook, the authorized companion of Grain Brain--both early printings of the first edition, 2013. By David Perlmutter, M.D. View Details


The Female Brain
by Louann Brizendine (Author)

Since Dr. Brizendine wrote The Female Brain ten years ago, the response has been overwhelming. This New York Times bestseller has been translated into more than thirty languages, has sold nearly a million copies between editions, and has most recently inspired a romantic comedy starring Whitney Cummings and Sofia Vergara. And its profound scientific understanding of the nature and experience of the female brain continues to guide women as they pass through life stages, to help men better understand the girls and women in their lives, and to illuminate the delicate... View Details

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Confronting Stigma
Why do we harshly judge certain behaviors or conditions, making it harder to talk honestly about them? This hour, TED speakers confront stigmas around addiction, depression, HIV and sex work. Guests include journalist Johann Hari, TV/film producer and mental health advocate Nikki Webber Allen, HIV awareness educator Arik Hartmann, and sex worker and activist Juno Mac.
Now Playing: Science for the People

#461 Adhesives
This week we're discussing glue from two very different times. We speak with Dr. Jianyu Li about his research into a new type of medical adhesive. And Dr. Geeske Langejans explains her work making and investigating Stone Age and Paleolithic glues.