Featured Research

from universities, journals, and other organizations

Charting autism's neural circuitry: Deleting single gene results in autism-like behavior and immunosuppressant drug prevents symptoms

Date:
July 2, 2012
Source:
Harvard Medical School
Summary:
Deleting a single gene in the cerebellum of mice can cause key autistic-like symptoms, researchers have found. They also discovered that rapamycin, a commonly used immunosuppressant drug, prevented these symptoms.

Deleting a single gene in the cerebellum of mice can cause key autistic-like symptoms, researchers have found. They also discovered that rapamycin, a commonly used immunosuppressant drug, prevented these symptoms.

The deleted gene is associated with Tuberous Sclerosis Complex (TSC), a rare genetic condition. Since nearly 50 percent of all people with TSC develop autism, the researchers believe their findings will help us better understand the condition's development.

"We are trying to find out if there are specific circuits in the brain that lead to autism-spectrum disorders in people with TSC," said Mustafa Sahin, Harvard Medical School associate professor of neurology at Boston Children's Hospital and senior author on the paper. "And knowing that deleting the genes associated with TSC in the cerebellum leads to autistic symptoms is a vital step in figuring out that circuitry."

This is the first time researchers have identified a molecular component for the cerebellum's role in autism. "What is so remarkable is that loss of this gene in a particular cell type in the cerebellum was sufficient to cause the autistic-like behaviors," said Peter Tsai, HMS instructor of neurology and the first author of this particular study.

These findings were published online July 1 in Nature.

TSC is a genetic disease caused by mutations in either one of two genes, TSC1 and TSC2. Patients develop benign tumors in various organs in the body, including the brain, kidneys and heart, and often suffer from seizures, delayed development and behavioral problems.

Researchers have known that there was a link between TSC genes and autism, and have even identified the cerebellum as the key area where autism and related conditions develop.

In both cases, deleting this gene caused the three main signs of autistic-like behaviors:

  • Abnormal social interactions. The mice spent less time with each other and more with inanimate objects, compared to controls.
  • Repetitive behaviors. The mice spent extended amounts of time pursuing one activity or with one particular object far more than normal.
  • Abnormal communication. Ultrasonic vocalizations, the communication technique among rodents, were highly distressed.

The researchers also tested learning. "These mice were able to learn new things normally," said Tsai, "but they had trouble with 'reversal learning,' or re-learning what they had learned when their environment changed."

Tsai and colleagues tested this by training the mice to swim a particular path in which a platform where they could rest was set up on one side of the pool. When the researchers moved the platform to the other side of the pool, the mice had greater difficulty than the control mice re-learning to swim to the other side.

"These changes in behavior indicate that the TSC1 gene in Purkinje cells, and by extension, the cerebellum, are a part of the circuitry for autism disorders," emphasized Sahin.

The researchers also found that the drug rapamycin averted the effects of the deleted gene. Administering the drug to the mice during development prevented the formation of autistic-like behaviors.

Currently, Sahin is the sponsor-principal investigator for an ongoing Phase II clinical trial to test the efficacy of everolimus, a compound in the same family as rapamycin, in improving neurocognition in children with TSC. The trial will be open for enrollment until December 2013.

"Our next step will be to see how the abnormalities in Purkinje cells affect autism-like development. We don't know how generalizable our current findings are, but understanding mechanisms beyond TSC genes might be useful to autism," said Tsai.

This study was supported by the National Institutes of Health (R01 NS58956), the John Merck Scholars Fund, Autism Speaks, Nancy Lurie Marks Family Foundation, Children's Hospital Boston Translational Research Program, the Children's Hospital Boston Mental Retardation and Developmental Disabilities Research Center (P30 HD18655).

Sahin serves as a consultant and site primary investigator for Novartis.


Story Source:

The above story is based on materials provided by Harvard Medical School. The original article was written by Shraddha Chakradhar. Note: Materials may be edited for content and length.


Journal Reference:

  1. Peter T. Tsai, Court Hull, YunXiang Chu, Emily Greene-Colozzi, Abbey R. Sadowski, Jarrett M. Leech, Jason Steinberg, Jacqueline N. Crawley, Wade G. Regehr, Mustafa Sahin. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature, 2012; DOI: 10.1038/nature11310

Cite This Page:

Harvard Medical School. "Charting autism's neural circuitry: Deleting single gene results in autism-like behavior and immunosuppressant drug prevents symptoms." ScienceDaily. ScienceDaily, 2 July 2012. <www.sciencedaily.com/releases/2012/07/120702210303.htm>.
Harvard Medical School. (2012, July 2). Charting autism's neural circuitry: Deleting single gene results in autism-like behavior and immunosuppressant drug prevents symptoms. ScienceDaily. Retrieved October 1, 2014 from www.sciencedaily.com/releases/2012/07/120702210303.htm
Harvard Medical School. "Charting autism's neural circuitry: Deleting single gene results in autism-like behavior and immunosuppressant drug prevents symptoms." ScienceDaily. www.sciencedaily.com/releases/2012/07/120702210303.htm (accessed October 1, 2014).

Share This



More Mind & Brain News

Wednesday, October 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

App Teaches Kindergarteners to Code

App Teaches Kindergarteners to Code

AP (Oct. 1, 2014) They can't all read yet, but soon kindergarteners may be able to create basic computer code. Researchers in Massachusetts developed an app that teaches young kids a simple computer programming language. (Oct. 1) Video provided by AP
Powered by NewsLook.com
Do Video Games Trump Brain Training For Cognitive Boosts?

Do Video Games Trump Brain Training For Cognitive Boosts?

Newsy (Sep. 29, 2014) More and more studies are showing positive benefits to playing video games, but the jury is still out on brain training programs. Video provided by Newsy
Powered by NewsLook.com
Your Spouse's Personality May Influence Your Earnings

Your Spouse's Personality May Influence Your Earnings

Newsy (Sep. 26, 2014) Research from Washington University suggest people with conscientious spouses have greater career success. Video provided by Newsy
Powered by NewsLook.com
Can A Blood Test Predict Psychosis Risk?

Can A Blood Test Predict Psychosis Risk?

Newsy (Sep. 26, 2014) Researchers say certain markers in the blood can predict risk of psychosis later in the life. The test can aid in early treatment for the condition. 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:

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