Featured Research

from universities, journals, and other organizations

Antioxidant treatment may help NF1-linked behavioral issues

Date:
September 12, 2013
Source:
Cincinnati Children's Hospital Medical Center
Summary:
New research in mouse models suggests that treatment with antioxidants may help reduce behavioral issues linked to the genetic nervous system disorder Neurofibromatosis 1 (NF1) and an associated condition called Costello syndrome.

New research in mouse models suggests that treatment with antioxidants may help reduce behavioral issues linked to the genetic nervous system disorder Neurofibromatosis 1 (NF1) and an associated condition called Costello syndrome.

Scientists from Cincinnati Children's Hospital Medical Center report their findings Sept. 12 in Cell Reports. The authors show that defects in the NF1/Ras molecular pathway, which cause the disorders, trigger production of harmful oxidative nitric oxide molecules in the oligodendrocyte glial brain cells of mice.

Part of the central nervous system, glial cells produce a substance called myelin, which provides a sheath along nerves that acts as a form of electrical insulation. Increased production of nitric oxide in the tested mice disrupted the tight structure of proteins and related components that make up the myelin sheath. It also damaged vasculature surrounding astrocyte cells and endothelial tissue. Altogether, these changes altered the permeability of the blood brain barrier.

According to researchers, affected mice had enlarged mutant white brain matter, enlarged optic nerves and exhibited hyperactive behavior. Levels of nitric oxide synthases (an enzyme that causes production nitric oxide) were significantly up-regulated in the mutant white matter.

Hyperactivity is present in up to 60 percent of people with NF1or a Rasopathy like Costello syndrome. A Rasopathy is a condition fueled by disruptions in the Ras molecular pathway. In their study, the authors tested mice bred to model both human NF1 and Costello syndrome.

"Our data provide a potential cellular and molecular mechanism of Rasopathy brain abnormalities, and we show that treatment with a broad spectrum antioxidant reverses the disruption of affected tissues and improves hyperactive behavior," said Nancy Ratner, PhD, senior investigator and a researcher in the Division of Experimental Hematology/Cancer Biology at Cincinnati Children's. "It will be interesting to see if people with Rasopathy exhibit the same white matter enlargement and cellular features we identified in our laboratory tests."

To treat the mice, researchers used a broad spectrum antioxidant called NAC, or N-Acetyl Cysteine, in the animals' drinking water. After six weeks of exposure to NAC, both the mouse models of NF1 and Costello syndrome improved. Abnormal cellular and tissue structure were reversed and hyperactive behavior subsided, according to researchers. The reversal of symptoms was more pronounced in the Costello animals than the NF1 animals.

The authors said they induced the structural deficiencies in the oligodendrocytes of both immature and mature adult mice. In both instances, researchers were able to use NAC treatment to reverse symptoms during adulthood, suggesting the brain defects are not linked to early life developmental processes.

When researchers gave the same antioxidant treatment to normal wild type mice, it caused the blood brain barrier to open and harmed the compact structure of myelin. Researchers said this shows high levels of antioxidant treatment in animals without elevated reactive oxygen levels can be detrimental.

People with NF1 can suffer from a number of cognitive and behavioral deficits and the current study sheds important new light on molecular processes that may drive these deficits. At the same time, authors cautioned that laboratory studies involving mouse models do not necessarily translate to treatment of human disease and additional study is needed.

A key collaborator in the study was first author Debra Mayes, PhD, a research fellow in the Ratner laboratory.


Story Source:

The above story is based on materials provided by Cincinnati Children's Hospital Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Debra A. Mayes, Tilat A. Rizvi, Haley Titus-Mitchell, Rachel Oberst, Georgianne M. Ciraolo, Charles V. Vorhees, Andrew P. Robinson, Stephen D. Miller, Jose A. Cancelas, Anat O. Stemmer-Rachamimov, Nancy Ratner. Nf1 Loss and Ras Hyperactivation in Oligodendrocytes Induce NOS-Driven Defects in Myelin and Vasculature. Cell Reports, September 2013 DOI: 10.1016/j.celrep.2013.08.011

Cite This Page:

Cincinnati Children's Hospital Medical Center. "Antioxidant treatment may help NF1-linked behavioral issues." ScienceDaily. ScienceDaily, 12 September 2013. <www.sciencedaily.com/releases/2013/09/130912132138.htm>.
Cincinnati Children's Hospital Medical Center. (2013, September 12). Antioxidant treatment may help NF1-linked behavioral issues. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2013/09/130912132138.htm
Cincinnati Children's Hospital Medical Center. "Antioxidant treatment may help NF1-linked behavioral issues." ScienceDaily. www.sciencedaily.com/releases/2013/09/130912132138.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins