Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists prevent cerebral palsy-like brain damage in mice

03.11.2011
Scientists at Washington University School of Medicine in St. Louis have shown that a protein may help prevent the kind of brain damage that occurs in babies with cerebral palsy.

Using a mouse model that mimics the devastating condition in newborns, the researchers found that high levels of the protective protein, Nmnat1, substantially reduce damage that develops when the brain is deprived of oxygen and blood flow. The finding offers a potential new strategy for treating cerebral palsy as well as strokes, and perhaps Alzheimer's, Parkinson's and other neurodegenerative diseases. The research is reported online in the Proceedings of the National Academy of Sciences.

"Under normal circumstances, the brain can handle a temporary disruption of either oxygen or blood flow during birth, but when they occur together and for long enough, long-term disability and death can result," says senior author David M. Holtzman, MD, the Andrew and Gretchen Jones Professor and head of the Department of Neurology. "If we can use drugs to trigger the same protective pathway as Nmnat1, it may be possible to prevent brain damage that occurs from these conditions as well as from neurodegenerative diseases."

The researchers aren't exactly sure how Nmnat1 protects brain cells, but they suspect that it blocks the effects of the powerful neurotransmitter glutamate. Brain cells that are damaged or oxygen-starved release glutamate, which can overstimulate and kill neighboring nerve cells.

The protective effects of Nmnat1 were first identified five years ago by Jeff Milbrandt, MD, PhD, the James S. McDonnell Professor and head of genetics at Washington University, who showed the protein can prevent damage to peripheral nerves in the body's extremities. Phillip Verghese, PhD, a postdoctoral research associate in Holtzman's laboratory, wanted to see if the protein's protective effects extend to the brain.

"Cerebral palsy is sometimes attributable to brain injury that stems from inadequate oxygen and blood flow to the brain before, during or soon after birth," says first author Philip Verghese, PhD, a postdoctoral research associate in Holtzman's laboratory. "We wanted to see if those injuries still occur in the presence of increased levels of Nmnat1."

The researchers evaluated the effects of oxygen and blood flow deprivation in normal mice and in mice genetically engineered to produce higher-than-normal levels of Nmnat1.

As early as six hours later, the mice with enhanced Nmnat1 had markedly less injury to the brain.

A week later, when the researchers measured the amount of tissue atrophy in the brain, they found that mice with high Nmnat1 had experienced far less damage to key brain structures like the hippocampus and cortex, which are known to be injured in cerebral palsy.

In a series of follow-up studies with collaborators Jeff Neil, MD, PhD, the Allen P. and Josephine B. Green Professor of Neurology, and Yo Sasaki, PhD, research assistant professor of genetics, the scientists were surprised at what they saw.

MRI scans of the brain showed that Nmnat1 might be even more protective than the first experiment suggested. In mice with boosted Nmnat1 levels, the scans revealed little to no brain damage.

Laboratory studies of the brain cells indicated that Nmnat1 prevents a particular form of cell death.

"There are two types of injury in the developing brain from inadequate oxygen and blood flow," Holtzman explains. "One is necrosis, where cells swell rapidly, burst and die; another is apoptosis, where the cells shrink and die. We found that Nmnat1 prevents necrosis."

Necrosis is believed to be responsible for killing brain cells in ischemic stroke in adults, which temporarily cuts off oxygen and blood flow to the brain. Dying cells flood the surrounding area with a glutamate, which can harm nearby cells. When researchers simulated this process in a test tube, fewer brain cells died in the presence of high Nmnat1.

Scientists in Milbrandt's and Holtzman's laboratories are following up on several potential explanations for Nmnat1's protective effects. Holtzman plans to test the protein in other models of brain injuries and neurodegenerative diseases.

Verghese PB, Sasaki Y, Donghan Y, Stewart F, Sabar F, Finn MB, Wroge CM, Mennerick S, Neil JJ, MIlbrandt J, Holtzman DM. NAD-synthesizing enzyme nicotinamide mononucleotide adenylyl transferase 1 (Nmnat1) protects against acute neurodegeneratoin in developing CNS by inhibiting excitotoxic-necrotic cell death. Proceedings of the National Academy of Sciences, online Oct. 31, 2011.

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
21.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Nagoya physicists resolve long-standing mystery of structure-less transition

21.08.2017 | Materials Sciences

Chronic stress induces fatal organ dysfunctions via a new neural circuit

21.08.2017 | Health and Medicine

Scientists from the MSU studied new liquid-crystalline photochrom

21.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>