Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists restore crucial myelin in brains of mice

14.01.2004


Scientists for the first time have restored a crucial substance known as myelin in a widespread area of an animal’s brain, opening the door toward new ways to improve treatment of an assortment of "demyelinating" diseases as well as the side effects of such common conditions as high blood pressure and heart disease. The research by a team led by Steven Goldman, M.D., Ph.D., of the University of Rochester Medical Center, is in the January issue of Nature Medicine.



Using human brain cells, Goldman’s team was able to restore proper nerve function in nearly the entire brains of mice much more efficiently than has been done previously. While the work is years away from a clinical study in humans, it serves as a milestone for researchers seeking to use stem cells and related cells known as progenitors to treat human disease.

"The results are much better than we expected," says Goldman, who is professor of Neurology and chief of the department’s Division of Cell and Gene Therapy at Rochester. "The percentage of cells in this experiment that began producing myelin is extraordinary, probably thousands of times as many as in previous experiments."


The work has implications for a wide variety of children’s diseases known as pediatric leukodystrophies, where the myelin is damaged or doesn’t work correctly, such as Canavan disease, Krabbe disease, or Tay-Sachs disease.

"While these diseases are generally rare, there are a lot of them, and together they affect thousands of children and their families," says Goldman. "We’ve got a long ways to go, but we’re optimistic that these findings could make a difference in the lives of these patients."

The work focuses on myelin, the fatty substance that covers nearly all the nerve cells in our bodies – like insulation wrapped around a wire – and helps signals in the nervous system go from one point to another. When the myelin breaks down, as in multiple sclerosis or the leukodystrophies, electrical signals degrade. It’s as if a crisp and clear phone conversation between two people speaking on land lines suddenly becomes patchy, sporadic and intermittent, as if they were speaking on cell phones in a hilly area. The net result can be dementia, difficulty walking, trouble breathing – a problem with any normal activity, depending on which parts of the brain or nervous system are affected.

The team remyelinated the mice – restored the "insulation" to the brain cells– by injecting into the mice highly purified human "progenitor" cells, which ultimately evolve into the cells that make myelin. These cells are known as oligodendrocytes: While these and other types of glial cells aren’t as well known as information-processing brain cells called neurons, they are vital to the brain’s health.

"Neurons get all the press, but glial cells are crucial to our health," says Goldman.

The team studied 44 mice that were born without any myelin wrapped around their brain cells. Within 24 hours of their birth, scientists injected cells that become oligodendrocytes –myelin-producing cells – into one precisely selected site in the mice.

Scientists found that the cells quickly migrated extensively throughout the brain, then developed into oligodendrocytes that produced myelin which coated or "ensheathed" the axons of cells in the brain.

"These cells infiltrate exactly those regions of the brain where one would normally expect oligodendrocytes to be present," says Goldman. "As they spread, they begin creating myelin which wraps around and ensheaths the axons."

Goldman says that while scientists have used other methods during the past two decades to remyelinate neurons in small portions of the brains of mice, the remyelination seen in the Nature Medicine paper is much more extensive. He estimates that about 10 percent of the axons in the mouse brains were remyelinated, compared to a tiny fraction of 1 percent in previous studies.

Currently, demyelinating diseases are permanent, and problems worsen as time goes on because there is no way to fix the underlying problem – restoring the myelin around the axons of brain cells. Goldman is hopeful that infusion of cells like oligodendrocyte progenitors might be used to offer relief to patients.

"The implantation of oligodendrocyte progenitors could someday be a treatment strategy for these diseases," says Goldman, a neurologist whose research was supported by the National Multiple Sclerosis Society and the National Institute of Neurological Diseases and Stroke. While the experiment provides hope for patients, Goldman says that further studies are necessary before considering a test in humans. Currently he’s conducting experiments in an attempt to remyelinate not just the brains but the entire nervous system of mice.

In addition to MS, many diseases affecting tens of millions of people in the United States involve myelin problems, Goldman says. These include widespread diseases like diabetes, heart disease and high blood pressure, where decreased blood flow can damage myelin and hurt brain cells, as well as strokes, which often destroy brain cells in part by knocking out the cells that pump out myelin. In addition, cerebral palsy is largely caused by a myelin problem in infants born prematurely.

The team found that adult human cells were much more adept at settling into the brain, becoming oligodendrocytes and producing myelin than the fetal cells. After just four weeks, adult cells but not fetal cells were producing myelin. After 12 weeks, four times as many oligodendrocytes derived from adult cells were producing myelin – 40 percent, compared to 10 percent of the cells from fetal cells. In addition, adult cells were likely to take root and form oligodendrocytes, not other brain cells such as neurons or astrocytes, which are not necessary for myelin production. On average, each oligodendrocyte from an adult cell successfully remyelinated five axons, compared to just one axon for fetal cells.

"The adult-acquired cells not only myelinate much more quickly, but more extensively – they myelinate many more axons per cell, and they do so with much higher efficiency. The adult cells were far more efficient than fetal cells at getting the job done," Goldman says.

An expert on the brain’s stem and progenitor cells, Goldman in 1999 isolated the cell that produces the oligodendrocyte, becoming the first person to isolate a progenitor cell in the brain (both stem cells and progenitor cells can develop into different types of cells, but unlike stem cells, progenitors cannot renew themselves indefinitely.). Later his team discovered that the cell is "multi-potential" – it can evolve into an oligodendrocyte, a neuron, or an astrocyte, depending on the timing and environment of a particular section of the brain.

Besides Goldman, other authors of the Nature Medicine paper include Martha Windrem, Ph.D., of the University of Rochester; Marta Nunes, William Rashbaum, Theodore Schwartz, and Neeta Roy of Cornell; and Robert Goodman and Guy McKhann II of Columbia University Medical School.

Tom Rickey | EurekAlert!
Further information:
http://www.urmc.rochester.edu/

More articles from Health and Medicine:

nachricht Using fragment-based approaches to discover new antibiotics
21.06.2018 | SLAS (Society for Laboratory Automation and Screening)

nachricht Scientists learn more about how gene linked to autism affects brain
19.06.2018 | Cincinnati Children's Hospital Medical Center

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: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>