Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists learn more about how gene linked to autism affects brain

19.06.2018

Study suggests modulating CHD8 might help some people with complex condition

New preclinical research shows a gene already linked to a subset of people with autism spectrum disorder is critical to healthy neuronal connections in the developing brain, and its loss can harm those connections to help fuel the complex developmental condition.


This microscopic image shows the presence of basic myelin protein and normal oligodendrocyte cell differentiation in the brain of a mouse. The cells form a protective sheath of insulation around nerves in the outer layers of the brain. Researchers report in Developmental Cell that mutation or loss of a gene called CHD8 hinders formation of the sheath in developing oligodendrocytes, causing neurological defects in the animals. CHD8 is one of the highest risk-susceptibility genes for autism.

Credit: Cincinnati Children's

Scientists at Cincinnati Children's Hospital Medical Center report in Developmental Cell their data clarify the biological role of the gene CHD8 and its protein CHD8 in developing oligodendrocytes, cells that form a protective insulation around nerves. The sheath supports neuronal connections in the brain and manifest themselves in white matter.

Although previous studies show disruptive mutations in CHD8 cause autism spectrum disorders (ASDs) and abnormalities in the brain's white matter, the underlying biology has been a mystery.

... more about:
»autism spectrum »genes »oligodendrocytes

The current study, published online June 18, shows that disruption of CHD8 hinders the production and maintenance of nerve insulation--harming the brain's neuronal connections and contributing to white matter damage. In laboratory mouse models genetically engineered to not express the CHD8 protein in the oligodendrocytes, the animals exhibited behavioral anomalies and seizures, according to lead study investigator Q. Richard Lu, PhD, Division of Experimental Hematology and Cancer Biology.

"So far no treatment is available for autism patients with mutations in CHD8, one of the highest risk-susceptibility genes for autism," Lu said. "Current studies are still at a very early stage in terms of therapeutic agents, but our findings present a potential strategy to restore the function of faulty CHD8-dependent processes."

Reversing Damage

Scientists found the strategy by using a number of experimental procedures with mice, including ChIP-Seq analysis of specific DNA-binding sites in developing oligodendrocytes, which helped them unravel biological processes. Their data showed that CHD8 loss or mutation reduces the function of what is known as a histone methyltransferase, which helps activate target genes needed for oligodendrocyte development.

They then figured out that using an experimental compound (CPI-455), which inhibits a different molecule linked to CHD8 called histone demethylase, rescued the development of oligodendrocytes. This reversed white matter defects in CHD8-mutant mice and reduced neurological problems in the animals.

Lu said the findings suggest that modulating the activity of CHD8 and the molecules that control it has the potential to enhance the generation of neuronal insulation in people with ASDs. He also stressed it will be years before knowing if the research will translate to clinical care in patients.

Additional studies are needed to verify the current study's findings, identify a suitable drug, and test its safety and effectiveness in laboratory models.

Unlocking the Code

CHD8 functions in the cell nucleus. It essentially unlocks the double-helix structure in the nucleus that contains DNA and RNA coding molecules. This allows changes to the helix's genetic and molecular composition that support the development of oligodendrocytes and nerve insulation by regulating levels of encoded gene products.

When mutations or loss of CDH8 occur, it results in harmful remodeling of molecular components in the helix (referred to as chromatin).

###

Funding support for the research came in part from: National Institutes of Health (R01NS072427, R01NS075243); the National Multiple Sclerosis Society (RG1508, NMSS RG-1501-02851); the CHARGE syndrome Foundation; the National Natural Science Foundation of China (81720108018); and the Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques (ARSEP, 2014, 2015, 2017).

The study included collaboration from co-authors at the Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai, China; Sorbonne Université, UPMC University Paris and Inserm GH Pitié-Salpêtrière, Institut du Cerveau et de la Moelle Épinière, Paris, France; and the departments of Pediatrics and Human Genetics at the University of Michigan in Ann Arbor.

Nick Miller | EurekAlert!
Further information:
http://dx.doi.org/10.1016/j.devcel.2018.05.022

Further reports about: autism spectrum genes oligodendrocytes

More articles from Health and Medicine:

nachricht The genes are not to blame
20.07.2018 | Technische Universität München

nachricht Targeting headaches and tumors with nano-submarines
20.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>