Enzyme in myelination process could lead to better understanding of neurological disorders

April 14, 2016, The Mount Sinai Hospital

The removal of the enzyme Dnmt1 during oligodendrocyte progenitor cell (OPC) differentiation in the central nervous system resulted in inefficient myelin formation and neurological deterioration, including loss of control of bodily movements, in mice, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published today in the medical journal Cell Reports. The results could lead to a new understanding of multiple sclerosis and other myelin disorders in humans.

Oligodendrocytes (OLs) are cells with the ability to form a specialized membrane that is called "myelin." Myelin is the insulating sheathing around the axons of nerve cells, which provides energetic support and allows for faster electrical impulse conduction. OLs are derived from progenitors called OPCs, which are stem-like cells with the ability to divide and generate OLs through a complex process of gene regulation.

This study shows that the development of OPCs into myelin-forming cells requires DNA methylation, which is a process consisting of the addition of chemical groups to the DNA carried out by enzymes called methyl transferases (DNMTs). When these groups are added, genes cannot be expressed and therefore are "silenced." The authors identify the many genes needed to be "silenced" in OPCs in order to allow for proper formation of myelin during development.

Researchers showed that the removal of Dnmt1 in oligodendrocyte lineage not only limited cell growth, but also led to cellular stress as well as severe and clinically symptomatic hypomelination - a reduced amount of myelin in nervous tissue. The mice experienced significant neurological symptoms, such as tremors and a loss of control of body movement, and eventually death.

"Our group has previously observed altered DNA methylation in the brain of patients with , the most devastating adult demyelinating disorder, but its role in myelin formation and the identity of the genes silenced by DNMT's in OPCs were not known," says lead investigator Patrizia Casaccia, MD, PhD, Professor of Neuroscience, Genetics and Genomics, and Neurology, and Chief of the Center of Excellence for Myelin Repair at the Friedman Brain Institute at the Icahn School of Medicine. "A better understanding of why DNA methylation is important for myelin formation and what genes need to be shut off during the formation of OLs from OPCs has important implications not only for development, but also for myelin repair."

The research could lead to the development of treatment for disorders where the is damaged and could also help in understanding how OPCs transform into brain cancer cells.

Further study is needed to understand the causes underlying aberrant DNA methylation in the brains of multiple sclerosis patients and in preclinical models. Translational applications will include the identification of factors that could bypass impaired DNA methylation.

Explore further: A supplement for myelin regeneration

Related Stories

A supplement for myelin regeneration

December 7, 2015
Multiple sclerosis patients continually lose the insulating myelin sheath that wraps around neurons and increases the speed of impulses in the central nervous system. Whenever neurons are demyelinated, OPCs migrate toward ...

Elucidation of the molecular mechanisms involved in remyelination

September 3, 2015
Researchers in Japan have revealed the molecular mechanism involved in the process of repair to damage of the myelin sheath.

Changes in nerve cells may contribute to the development of mental illness

November 28, 2012
Reduced production of myelin, a type of protective nerve fiber that is lost in diseases like multiple sclerosis, may also play a role in the development of mental illness, according to researchers at the Graduate School of ...

Myelin cells swing along blood vessels to traverse the brain

January 22, 2016
The cells that create myelin, a fatty material that insulates nerve fibers in the brain's white matter, migrate into the developing brain by climbing and swinging on blood vessels, according to new research led by UC San ...

Researchers discover dynamic behavior of progenitor cells in brain

May 9, 2013
By monitoring the behavior of a class of cells in the brains of living mice, neuroscientists at Johns Hopkins discovered that these cells remain highly dynamic in the adult brain, where they transform into cells that insulate ...

Recommended for you

New wearable brain scanner allows patients to move freely for the first time

March 21, 2018
A new generation of brain scanner, that can be worn like a helmet allowing patients to move naturally whilst being scanned, has been developed by researchers at the Sir Peter Mansfield Imaging Centre, University of Nottingham ...

International team confirms new genetic mutation link to amyotrophic lateral sclerosis

March 21, 2018
Kinesin family member 5A (KIF5A), a gene previously linked to two rare neurodegenerative disorders, has been definitively connected to amyotrophic lateral sclerosis (ALS) by an international team from several of the world's ...

New ALS gene points to common role of cytoskeleton in disease

March 21, 2018
An international team of researchers led by John Landers, PhD, at UMass Medical School, and Bryan Traynor, MD, PhD, at the National Institute on Aging at the National Institutes of Health (NIH), has identified KIF5A as a ...

Neuroscientists develop potential tools for the study of brain function

March 21, 2018
A team of University of Missouri neuroscientists are inching closer to developing the tools needed to decipher the brain. In 2015, the team received a National Science Foundation Early Concept Grant for Exploratory Research ...

Researchers listen for silent seizures with 'brain stethoscope' that turns brain waves into sound

March 21, 2018
When a doctor or nurse suspects something is wrong with a patient's heart, there's a simple way to check: put a stethoscope over the heart and listen to the sounds it makes. Doctors and nurses can use the same diagnostic ...

Amygdala neurons increase as children become adults—except in autism

March 20, 2018
In a striking new finding, researchers at the UC Davis MIND Institute found that typically-developing children gain more neurons in a region of the brain that governs social and emotional behavior, the amygdala, as they become ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.