Featured Research

from universities, journals, and other organizations

How Microscopic Changes To Brain Cause Schizophrenic Behavior In Mice

Date:
March 3, 2009
Source:
Scripps Research Institute
Summary:
Disrupting the function of a key molecule in the brain leads to microscopic brain abnormalities and schizophrenia-like behavior in mice. These abnormalities are similar to those seen in the autopsied brains of people who diagnosed with schizophrenia in life, according to a scientists.

"These findings in mice may help shed light on how schizophrenia, an often severe and debilitating disease, emerges in humans," says Ulrich Mueller (right), shown here with co-author Claudia Barros.

 Disrupting the function of a key molecule in the brain leads to microscopic brain abnormalities and schizophrenia-like behavior in mice. These abnormalities are similar to those seen in the autopsied brains of people who diagnosed with schizophrenia in life, according to a team of scientists at the Scripps Research Institute.

"We found several microscopic pathologies and behavioral traits that are hallmarks of schizophrenia, says Ulrich Mueller, Ph.D., a professor at Scripps Research who was senior author of the study. "These findings in mice may help shed light on how schizophrenia, an often severe and debilitating disease, emerges in humans."

In the study Mueller, Research Associate Claudia Barros, and colleagues also showed that the schizophrenic mice could recover normal behavior when treated with clozapine, a decades-old drug sometimes used to treat schizophrenia in people. This suggests that these mice might provide researchers with a good model system for studying schizophrenia and testing new drugs designed to treat people suffering from it.

Schizophrenia affects millions of Americans — about one percent of all people in the United States, according to the National Institute of Mental Health — and manifests in symptoms like hearing imaginary voices, paranoia, delusions of grandeur, severe apathy, and incoherent speech. Despite its prevalence, however, the causes of schizophrenia are not entirely understood.

The scientific consensus is that the disease results from a combination of genes and other factors. Schizophrenia runs in families, which is strong evidence that inherited genes play a role, but the disease is not completely genetic. Some identical twins, for instance, are discordant — one will have the disease while the other will not. The fact that it can strike one genetically identical twin to the exclusion of the other means that there are more than just genes involved. Development may be another factor.

People with schizophrenia usually do not begin showing signs of the disease until their late teens or early 20s. One of the current scientific hypotheses regarding schizophrenia, however, is that the disease is caused by developmental defects that occur in the brain long before the signs of the disease emerge. The mice that Mueller, Barros, and colleagues studied would seem to lend credence to this hypothesis.

In the new paper, the team describes what happens to the mice when they lose the function of a brain protein called neuregulin — an important developmental protein that helps the brain form its distinct structures early in development. Genetic studies have linked inherited forms of this protein and its receptors to schizophrenia and numerous other mental health problems.

Mueller, Barros, and colleagues managed to effectively remove the function of neuregulin by eliminating the receptor to which it binds. Because this is such an important developmental protein, they expected that eliminating its receptor would severely impact the development of the mouse's brain. To the researchers' surprise, that did not happen. Overall, the brains were normal. Microscopically, however, the loss of neuregulin tells another story.

To understand what happens when you hamper the action of neuregulin, Mueller says, you have to understand something about how neurons in the brain form and communicate. Humans, mice, and other mammals have brains that develop through multiple intricate stages, bursts, and crawls. Brain tissue first forms without neurons, as a sort of scaffold, and then the neurons grow, creep into place, and connect to each other.

When it is finished, the average human brain has some 100 billion neurons — a highly intricate, overlapping web of branched structures that communicate with one another (and the outside world). They have tree-like networks of extensions called "dendrites" that receive input from other neurons, as many as ten thousand inputs for a single neuron. The structure that enables one neuron to contact another is called a dendritic spine. These humble structures look like a little fingers coming off the dendrites, and their proper formation may be one of the keys to schizophrenia.

In their study, the scientists discovered that when mice are deprived of neuregulin, their dendritic spines start to form, but do not mature completely — instead falling apart while the brain matures. The effect of this loss is evident in behavior tests, where mice display hallmarks of schizophrenia, such as social interaction problems and reduced anxiety. Loss of the spines also leads to the loss of the ability to adapt to and anticipate a startling noise — a classic sign of a schizophrenia-like state in mice.

This study provides support for a hypothesis about schizophrenia that implicates what are known as "glutamatergic" neurons. All neurons communicate by releasing particular chemicals called neurotransmitters into synapses, the tiny gaps in between two neurons. One longstanding hypothesis concerning schizophrenia implicates neurons that release the neurotransmitter dopamine. Another hypothesis is that glutamatergic neurons, which release the neurotransmitter glutamate, are also important in schizophrenia. The study supports the second hypothesis, says Mueller, because the mice had problems with their glutamatergic synapses, which are located at dendritic spines.

This work was supported by the National Institutes of Health, by a Christopher Reeve Foundation fellowship, by support given by the American Health Assistant Foundation, and through a Basque Government fellowship.


Story Source:

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


Journal Reference:

  1. Ulrich Mueller, Claudia Barros, Pablo Chamero, Amanda J. Roberts, Ed Korzus, Lisa Stowers, Mark Mayford, Barbara Calabrese, Shelley Halpain and Kent Lloyd. Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system. Proceedings of the National Academy of Sciences, Feb 17, 2009

Cite This Page:

Scripps Research Institute. "How Microscopic Changes To Brain Cause Schizophrenic Behavior In Mice." ScienceDaily. ScienceDaily, 3 March 2009. <www.sciencedaily.com/releases/2009/02/090219121329.htm>.
Scripps Research Institute. (2009, March 3). How Microscopic Changes To Brain Cause Schizophrenic Behavior In Mice. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2009/02/090219121329.htm
Scripps Research Institute. "How Microscopic Changes To Brain Cause Schizophrenic Behavior In Mice." ScienceDaily. www.sciencedaily.com/releases/2009/02/090219121329.htm (accessed August 21, 2014).

Share This




More Mind & Brain News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Do More Wedding Guests Make A Happier Marriage?

Do More Wedding Guests Make A Happier Marriage?

Newsy (Aug. 20, 2014) — A new study found couples who had at least 150 guests at their weddings were more likely to report being happy in their marriages. Video provided by Newsy
Powered by NewsLook.com
Charter Schools Alter Post-Katrina Landscape

Charter Schools Alter Post-Katrina Landscape

AP (Aug. 20, 2014) — Nine years after Hurricane Katrina, charter schools are the new reality of public education in New Orleans. The state of Louisiana took over most of the city's public schools after the killer storm in 2005. (Aug. 20) Video provided by AP
Powered by NewsLook.com
Researcher Testing on-Field Concussion Scanners

Researcher Testing on-Field Concussion Scanners

AP (Aug. 19, 2014) — Four Texas high school football programs are trying out an experimental system designed to diagnose concussions on the field. The technology is in response to growing concern over head trauma in America's most watched sport. (Aug. 19) Video provided by AP
Powered by NewsLook.com
Kids' Drawings At Age 4 Linked To Intelligence At Age 14

Kids' Drawings At Age 4 Linked To Intelligence At Age 14

Newsy (Aug. 19, 2014) — A study by King's College London says there's a link between how well kids draw at age 4 and how intelligent they are later in life. 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