Featured Research

from universities, journals, and other organizations

Inhibitory neurons key to understanding neuropsychiatric disorders

Date:
November 11, 2010
Source:
Baylor College of Medicine
Summary:
In 1999, researchers identified mutations in a gene called MECP2 as the culprit in a devastating neurological disorder called Rett syndrome. In new research the same scientists demonstrate that the loss of the protein MeCP2 in a special group of inhibitory nerve cells in the brain reproduces nearly all Rett syndrome features.

The brain works because 100 billion of its special nerve cells called neurons regulate trillions of connections that carry and process information. The behavior of each neuron is precisely determined by the proper function of many genes.

In 1999, Baylor College of Medicine researcher Dr. Huda Zoghbi and her colleagues identified mutations in one of these genes called MECP2 as the culprit in a devastating neurological disorder called Rett syndrome . In new research in mice published in the current issue of the journal Nature, Zoghbi and her colleagues demonstrate that the loss of the protein MeCP2 in a special group of inhibitory nerve cells in the brain reproduces nearly all Rett syndrome features.

Children, mostly girls, born with Rett syndrome, appear normal at first, but stop or slow intellectual and motor development between three months and three years of age, losing speech, developing learning and gait problems. Some of their symptoms resemble those of autism.

These inhibitory (gamma-amino-butyric-acid [GABA]-ergic) neurons make up only 15 to 20 percent of the total number of neurons in the brain. Loss of MeCP2 causes a 30 to 40 percent reduction in the amount of GABA, the specific signaling chemical made by these neurons. This loss impairs how these neurons communicate with other neurons in the brain. These inhibitory neurons keep the brakes on the communication system, enabling proper transfer of information.

"In effect, the lack of MeCP2 impairs the GABAergic neurons that are key regulators governing the transfer of information in the brain," said Dr. Hsiao-Tuan Chao, an M.D./Ph.D student in Zoghbi's laboratory and first author of the report.

Chao made the discovery by developing a powerful new tool or mouse model that allowed researchers to remove MeCP2 from only the GABAergic neurons.

"We did this study thinking that perhaps all we would see was a few symptoms of Rett syndrome," said Chao. "Strikingly, we saw that removing MeCP2 solely from GABAergic neurons reproduced almost all the features of Rett syndrome, including cognitive deficits, breathing difficulties, compulsive behavior, and repetitive stereotyped movements. The study tells us that MeCP2 is a key protein for the function of these neurons."

Once the authors determined that the key problem rested with the GABAergic neurons, they sought to find out how the lack of MeCP2 disturbed the function of these neurons. Chao discovered that losing MeCP2 caused the GABAergic neurons to release less of the neurotransmitter, GABA. This occurs because losing MeCP2 reduces the amount of the enzymes required for the production of GABA.

Intriguingly, prior studies showed that expression of these enzymes is also reduced in some patients with autism, schizophrenia and bipolar disorder, said Chao.

"This tells us a lot about what is going on in the brains of people with Rett syndrome, autism or even schizophrenia," said Chao. "A child is born healthy. She starts to grow and then begins to lose developmental milestones. Communication between neurons is impaired, in part due to reduced signals from GABAergic neurons."

"This study taught us that an alteration in the signal from GABAergic neurons is sufficient to produce features of autism and other neuropsychiatric disorders," said Zoghbi, a Howard Hughes Medical Institute investigator and director of the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital.

Others who took part in this work include Hongmei Chen, Rodney C. Samaco, Mingshan Xue, Maria Chahrour, Jong Yoo, Jeffrey L. Neul, Hui-Chen Lu, Jeffrey L. Noebels and Christian Rosenmund, all of BCM, John L.R. Rubenstein of University of Calfornia in San Francisco, Marc Ekker of University of Ottawa in Ontario, and Shiaoching Gong and Nathaniel Heintz of The Rockefeller University in New York.

Funding for this work came from the Howard Hughes Medical Institute, the National Institute of Neurological Disorders and Stroke, the Simons Foundation, the Rett Syndrome Research Trust, the Intellectual and Developmental Disability Research Centers, the International Rett Syndrome Foundation, Autism Speaks, the National Institute of Mental Health, Baylor Research Advocates for Student Scientists and McNair Fellowships.


Story Source:

The above story is based on materials provided by Baylor College of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Hsiao-Tuan Chao, Hongmei Chen, Rodney C. Samaco, Mingshan Xue, Maria Chahrour, Jong Yoo, Jeffrey L. Neul, Shiaoching Gong, Hui-Chen Lu, Nathaniel Heintz, Marc Ekker, John L. R. Rubenstein, Jeffrey L. Noebels, Christian Rosenmund, Huda Y. Zoghbi. Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature, 2010; 468 (7321): 263 DOI: 10.1038/nature09582

Cite This Page:

Baylor College of Medicine. "Inhibitory neurons key to understanding neuropsychiatric disorders." ScienceDaily. ScienceDaily, 11 November 2010. <www.sciencedaily.com/releases/2010/11/101110131155.htm>.
Baylor College of Medicine. (2010, November 11). Inhibitory neurons key to understanding neuropsychiatric disorders. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2010/11/101110131155.htm
Baylor College of Medicine. "Inhibitory neurons key to understanding neuropsychiatric disorders." ScienceDaily. www.sciencedaily.com/releases/2010/11/101110131155.htm (accessed October 20, 2014).

Share This



More Mind & Brain News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Court Ruling Means Kids' Online Activity Could Be On Parents

Court Ruling Means Kids' Online Activity Could Be On Parents

Newsy (Oct. 17, 2014) In a ruling attorneys for both sides agreed was a first of its kind, a Georgia appeals court said parents can be held liable for what kids put online. Video provided by Newsy
Powered by NewsLook.com
The Best Foods To Boost Your Mood

The Best Foods To Boost Your Mood

Buzz60 (Oct. 17, 2014) Feeling down? Reach for the refrigerator, not the medicine cabinet! TC Newman (@PurpleTCNewman) shares some of the best foods to boost your mood. Video provided by Buzz60
Powered by NewsLook.com
You Can Get Addicted To Google Glass, Apparently

You Can Get Addicted To Google Glass, Apparently

Newsy (Oct. 15, 2014) Researchers claim they’ve diagnosed the first example of the disorder in a 31-year-old U.S. Navy serviceman. Video provided by Newsy
Powered by NewsLook.com
First Confirmed Case Of Google Glass Addiction

First Confirmed Case Of Google Glass Addiction

Buzz60 (Oct. 15, 2014) A Google Glass user was treated for Internet Addiction Disorder caused from overuse of the device. Morgan Manousos (@MorganManousos) has the details on how many hours he spent wearing the glasses, and what his symptoms were. Video provided by Buzz60
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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