Researchers uncover mechanisms of common inherited mental retardation

January 8, 2008
Researchers uncover mechanisms of common inherited mental retardation
Dr. Kimberly Huber investigated how Fragile X syndrome affects communication between cells in the hippocampus, a region of the brain that is involved in learning and memory. Fragile X syndrome is the most common cause of inherited mental retardation and the most common genetic cause of autism. Credit: UT Southwestern Medical Center

Researchers at UT Southwestern Medical Center are uncovering how brain cells are affected in Fragile X syndrome, the most common cause of inherited mental retardation and the most common genetic cause of autism.

“I think we’ve discovered a core mechanism underlying Fragile X syndrome,” said Dr. Kimberly Huber, assistant professor of neuroscience and senior author of a study appearing in Wednesday’s edition of the Journal of Neuroscience.

Dr. Huber’s research with mice focuses on how Fragile X syndrome affects communication between cells in the hippocampus, a region of the brain that is involved in learning and memory. Her findings show that two different chemical signals go awry in Fragile X syndrome, indicating that drugs that interact with these signals might be a pathway to help treat the syndrome.

“The more we know about how signaling mechanisms in the brain lead to normal memory and learning, the better we can understand what goes wrong in conditions such as Fragile X syndrome,” said Dr. Huber, who is a Southwestern Medical Foundation Scholar in Medical Research. “Our research is laying the groundwork for such understanding and indicates a new area for research.”

Fragile X syndrome got its name because it affects a single gene, Fmr1, on the X chromosome. Under a microscope, the area around the gene looks narrower than normal, or “fragile.” According to the Centers for Disease Control and Prevention, the syndrome, which mostly occurs in males, affects about one in every 4,000 white males in the U.S.

It often causes a distinct physical appearance including an elongated face with protruding ears, hyperflexible joints, and mental deficits ranging from mood disorders to severe mental retardation. Much of the current treatment focuses on behavioral therapy combined with medications to control mood and seizures.

Dr. Huber previously co-discovered that mice genetically engineered to lack Fmr1 have a defective signaling system in the brain that controls learning in the hippocampus. This system relies on a chemical messenger called glutamate, which under normal circumstances causes nerve cells to make proteins and change their electrical firing patterns in response to learning situations. Without a properly working Fmr1 gene, the glutamate signaling system malfunctions.

In 2007 she and colleagues at UT Southwestern found that acetylcholine, another specific signaling chemical, affects the same protein-making factory that glutamate does. This research appeared in the Oct. 24, 2007, issue of the Journal of Neuroscience.

“We suggest that treatment that affects the acetylcholine system might be a supplement or alternative to drugs targeting the glutamate pathway,” Dr. Huber said.

In the current study, she and postdoctoral researcher Dr. Jennifer Ronesi investigated a protein, called Homer, which serves as a kind of structural support for the glutamate system. The Homer–glutamate support system is disconnected in Fragile X syndrome. Dr. Huber’s group discovered that this disconnection results in an inability of brain cells to make the new proteins important for learning and memory.

Source: UT Southwestern Medical Center

Explore further: New explanation offered for symptoms of fragile X syndrome

Related Stories

New explanation offered for symptoms of fragile X syndrome

September 20, 2016

Until recently, scientists thought they understood one of the underlying causes of fragile X syndrome, the most common inherited cause of intellectual disability in the United States. The syndrome, which is associated with ...

Study implicates glial cells in fragile X syndrome

October 4, 2016

Research on fragile X syndrome, the most common inherited cause of mental retardation, has focused mostly on how the genetic defect alters the functioning of neurons in the brain. A new study focusing on a different type ...

New genetic clues found in fragile X syndrome

January 16, 2015

Scientists have gained new insight into fragile X syndrome—the most common cause of inherited intellectual disability—by studying the case of a person without the disorder, but with two of its classic symptoms.

Statins suppress Rett syndrome symptoms in mice

July 29, 2013

Statins, a class of cholesterol-lowering drugs found in millions of medicine cabinets, may help treat Rett Syndrome, according to a study published today in Nature Genetics. The Rett Syndrome Research Trust (RSRT) funded ...

Recommended for you

Artificial beta cells

December 8, 2016

Researchers led by ETH Professor Martin Fussenegger at the Department of Biosystems Science and Engineering (D-BSSE) in Basel have produced artificial beta cells using a straightforward engineering approach.

Key regulator of bone development identified

December 8, 2016

Loss of a key protein leads to defects in skeletal development including reduced bone density and a shortening of the fingers and toes—a condition known as brachydactyly. The discovery was made by researchers at Penn State ...

Researchers question lifelong immunity to toxoplasmosis

December 8, 2016

Medical students are taught that once infected with Toxoplasma gondii—the "cat parasite"—then you're protected from reinfection for the rest of your life. This dogma should be questioned, argue researchers in an Opinion ...

TET proteins drive early neurogenesis

December 7, 2016

The fate of stem cells is determined by series of choices that sequentially narrow their available options until stem cells' offspring have found their station and purpose in the body. Their decisions are guided in part by ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.