Featured Research

from universities, journals, and other organizations

Could Schizophrenia Arise From A Single Defect?

Date:
March 2, 2005
Source:
Cell Press
Summary:
Researchers have long puzzled over the apparently multiple causes of complex developmental disorders such as schizophrenia. Individuals seem to be predisposed to the disease by a tragic, mysterious combination of genetics, prenatal trauma, viral infection, and early experience. And its array of symptoms--including hallucinations, delusions, paranoia, and antisocial behavior--has defied simple explanation.

Researchers have long puzzled over the apparently multiple causes of complex developmental disorders such as schizophrenia. Individuals seem to be predisposed to the disease by a tragic, mysterious combination of genetics, prenatal trauma, viral infection, and early experience. And its array of symptoms--including hallucinations, delusions, paranoia, and antisocial behavior--has defied simple explanation.

In experiments with rats, however, researchers led by led by Gerard J.M. Martens of the Nijmegen Center for Molecular Life Sciences (NCMLS) have demonstrated that such seemingly diverse combinations of symptoms can arise from a subtle imbalance in the activity of a single gene whose protein plays a key role in neural development.

The researchers studied the genetic differences between rats bred to be either resistant or susceptible to the drug apomorphine. A long history of studies has revealed that apomorphine-susceptible rats show many behavioral and biochemical differences from normal rats. What's more, the tendency to develop these differences depends on their exposure to stress in early life.

To search for genetic differences between the two types of rats, the researchers used microarrays, or so-called "gene chips," to analyze the activity of thousands of genes in the rats' brains. To their surprise, they discovered only a single genetic difference between the two groups of rats. The levels of activity of a gene called Aph-1b tended to be lower in the susceptible rats than in the non-susceptible rats. Importantly, this gene produces a protein that is a component of an enzyme called g-secretase, which plays a role in regulating many processes in the developing brain. The researchers found that, as a result of this lower level of Aph-1b protein, g-secretase showed reduced activity in the brains of the susceptible rats.

What's more, when the researchers tested various behaviors of "sublines" of rats with different levels of Aph-1b, they found that their behaviors correlated with those levels--termed a "gene dosage effect."

"Thus, a subtle imbalance in the expression of a single gene product that is involved in a wide variety of developmental signaling pathways may well constitute the molecular basis of a complex phenotype that is generally believed to have a multifactorial background," concluded the scientists.

###

The researchers include Marcel W. Coolen, Karen M.J. Van Loo, Nick N.H.M. Van Bakel, and Gerard J.M. Martens of the Nijmegen Center for Molecular Life Sciences (NCMLS) and Institute for Neuroscience at Radboud University Nijmegen; David J. Pulford of Target Discovery at Organon Laboratories Limited; Lutgarde Serneels and Bart De Strooper of the Flanders Interuniversity Institute for Biotechnology (VIB) and Center for Human Genetics at Katholieke Universiteit Leuven; and Bart A. Ellenbroek and Alexander R. Cools of Nijmegen Institute for Neurosciences (NIN) at Radboud University Nijmegen. This work received support from the Netherlands Organization for Scientific Research (NWO). B.D.S. was supported by a Pioneer award from the Alzheimer's Association, grant IUAP P5/9, and EU contract LSHM-CT-2003-503330 (APOPIS).

Marcel W. Coolen, Karen M.J. Van Loo, Nick N.H.M. Van Bakel, David J. Pulford, Lutgarde Serneels, Bart De Strooper, Bart A. Ellenbroek, Alexander R. Cools, and Gerard J.M. Martens: "Gene dosage effect on -secretase component Aph-1b in a rat model for neurodevelopmental disorders"

Publishing in Neuron, Volume 45, Number 4, February 17, 2005, pages 495-503.


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "Could Schizophrenia Arise From A Single Defect?." ScienceDaily. ScienceDaily, 2 March 2005. <www.sciencedaily.com/releases/2005/02/050223122011.htm>.
Cell Press. (2005, March 2). Could Schizophrenia Arise From A Single Defect?. ScienceDaily. Retrieved April 24, 2014 from www.sciencedaily.com/releases/2005/02/050223122011.htm
Cell Press. "Could Schizophrenia Arise From A Single Defect?." ScienceDaily. www.sciencedaily.com/releases/2005/02/050223122011.htm (accessed April 24, 2014).

Share This



More Health & Medicine News

Thursday, April 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Fungus Killing Bats, Spreading in US

Deadly Fungus Killing Bats, Spreading in US

AP (Apr. 24, 2014) A disease that has killed more than six million cave-dwelling bats in the United States is on the move and wildlife biologists are worried. White Nose Syndrome, discovered in New York in 2006, has now spread to 25 states. (April 24) Video provided by AP
Powered by NewsLook.com
Companies Ramp Up Wellness to Lower Health Costs

Companies Ramp Up Wellness to Lower Health Costs

AP (Apr. 24, 2014) That little voice telling you to exercise, get in shape and get healthy is probably coming from your boss. More companies are beefing up wellness programs to try and cut down their health care costs. (April 24) Video provided by AP
Powered by NewsLook.com
Blood From World's Oldest Woman Suggests Life Limit

Blood From World's Oldest Woman Suggests Life Limit

Newsy (Apr. 24, 2014) Scientists say for the extremely elderly, their stem cells might reach a state of exhaustion. This could limit one's life span. Video provided by Newsy
Powered by NewsLook.com
FDA Wants To Ban Sales Of E-Cigarettes To Minors

FDA Wants To Ban Sales Of E-Cigarettes To Minors

Newsy (Apr. 24, 2014) The Food and Drug Administration wants to crack down on the use of e-cigarettes, banning the sale of the product to minors. Video provided by Newsy
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