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 Uncuffing nitric oxide production: Beta-arrestin2 complexes regulate NO levels
05.06.2020 | Medical University of South Carolina

nachricht Diabetes mellitus: A risk factor for early colorectal cancer
27.05.2020 | Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg

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: Restoring vision by gene therapy

Latest scientific findings give hope for people with incurable retinal degeneration

Humans rely dominantly on their eyesight. Losing vision means not being able to read, recognize faces or find objects. Macular degeneration is one of the major...

Im Focus: Small Protein, Big Impact

In meningococci, the RNA-binding protein ProQ plays a major role. Together with RNA molecules, it regulates processes that are important for pathogenic properties of the bacteria.

Meningococci are bacteria that can cause life-threatening meningitis and sepsis. These pathogens use a small protein with a large impact: The RNA-binding...

Im Focus: K-State study reveals asymmetry in spin directions of galaxies

Research also suggests the early universe could have been spinning

An analysis of more than 200,000 spiral galaxies has revealed unexpected links between spin directions of galaxies, and the structure formed by these links...

Im Focus: New measurement exacerbates old problem

Two prominent X-ray emission lines of highly charged iron have puzzled astrophysicists for decades: their measured and calculated brightness ratios always disagree. This hinders good determinations of plasma temperatures and densities. New, careful high-precision measurements, together with top-level calculations now exclude all hitherto proposed explanations for this discrepancy, and thus deepen the problem.

Hot astrophysical plasmas fill the intergalactic space, and brightly shine in stellar coronae, active galactic nuclei, and supernova remnants. They contain...

Im Focus: Biotechnology: Triggered by light, a novel way to switch on an enzyme

In living cells, enzymes drive biochemical metabolic processes enabling reactions to take place efficiently. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics. Researchers now identified an enzyme that, when illuminated with blue light, becomes catalytically active and initiates a reaction that was previously unknown in enzymatics. The study was published in "Nature Communications".

Enzymes: they are the central drivers for biochemical metabolic processes in every living cell, enabling reactions to take place efficiently. It is this very...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

International Coral Reef Symposium in Bremen Postponed by a Year

06.04.2020 | Event News

 
Latest News

New image of a cancer-related enzyme in action helps explain gene regulation

05.06.2020 | Life Sciences

Silicon 'neurons' may add a new dimension to computer processors

05.06.2020 | Physics and Astronomy

Protecting the Neuronal Architecture

05.06.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>