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 New approach for targeted cancer immunotherapy
30.07.2020 | Universität Basel

nachricht A new way to target cancers using 'synthetic lethality'
28.07.2020 | University of California - San Diego

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: TU Graz Researchers synthesize nanoparticles tailored for special applications

“Core-shell” clusters pave the way for new efficient nanomaterials that make catalysts, magnetic and laser sensors or measuring devices for detecting electromagnetic radiation more efficient.

Whether in innovative high-tech materials, more powerful computer chips, pharmaceuticals or in the field of renewable energies, nanoparticles – smallest...

Im Focus: Tailored light inspired by nature

An international research team with Prof. Cornelia Denz from the Institute of Applied Physics at the University of Münster develop for the first time light fields using caustics that do not change during propagation. With the new method, the physicists cleverly exploit light structures that can be seen in rainbows or when light is transmitted through drinking glasses.

Modern applications as high resolution microsopy or micro- or nanoscale material processing require customized laser beams that do not change during...

Im Focus: NYUAD astrophysicist investigates the possibility of life below the surface of Mars

  • A rover expected to explore below the surface of Mars in 2022 has the potential to provide more insights
  • The findings published in Scientific Reports, Springer Nature suggests the presence of traces of water on Mars, raising the question of the possibility of a life-supporting environment

Although no life has been detected on the Martian surface, a new study from astrophysicist and research scientist at the Center for Space Science at NYU Abu...

Im Focus: Manipulating non-magnetic atoms in a chromium halide enables tuning of magnetic properties

New approach creates synthetic layered magnets with unprecedented level of control over their magnetic properties

The magnetic properties of a chromium halide can be tuned by manipulating the non-magnetic atoms in the material, a team, led by Boston College researchers,...

Im Focus: A new method to significantly increase the range and stability of optical tweezers

Scientists of Tomsk Polytechnic University jointly with a team of the V.E. Zuev Institute of Atmospheric Optics of the Siberian Branch of the Russian Academy of Sciences have discovered a method to increase the operation range of optical traps also known

Optical tweezers are a device which uses a laser beam to move micron-sized objects such as living cells, proteins, and molecules. In 2018, the American...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“Conference on Laser Polishing – LaP 2020”: The final touches for surfaces

23.07.2020 | Event News

Conference radar for cybersecurity

21.07.2020 | Event News

Contact Tracing Apps against COVID-19: German National Academy Leopoldina hosts international virtual panel discussion

07.07.2020 | Event News

 
Latest News

Time To Say Goodbye: The MOSAiC floe’s days are numbered

31.07.2020 | Earth Sciences

Scientists find new way to kill tuberculosis

31.07.2020 | Life Sciences

Spin, spin, spin: researchers enhance electron spin longevity

31.07.2020 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>