Mapping the neuron-behavior link in Rett Syndrome

A link between certain behaviors and the lack of the protein associated with Rett Syndrome – a devastating autism spectrum disorder – demonstrates the importance of MeCP2 (the protein) and reveals never-before recognized functions associated with aggression and obesity, said researchers at Baylor College of Medicine in a report in the current issue of the journal Neuron.

"This protein is critical for the proper function of majority of neurons," said Dr. Huda Y. Zoghbi, a BCM professor of pediatrics, neurology, neuroscience, molecular and human genetics and a Howard Hughes Medical Institute investigator who is senior author on the paper. Zoghbi and her laboratory discovered the Rett gene.

Rett Syndrome affects between 1 in 10,000 females who express a wide variety of symptoms, most of them neurological.

"Observe a girl with Rett Syndrome and you will see that she has most of the neurological symptoms you are familiar with," Zoghbi said. "There are movement problems, balance problems, tremor, seizures, autism, learning and memory problems, anxiety and even more."

Girls with Rett Syndrome lack MeCP2 (found on the X chromosome) in as many as 50 percent of their neurons. The severity and breadth of symptoms they experience depend on the percentage of neurons that lack the protein.

To determine which neurons affects which behaviors, Zoghbi and her colleagues engineered mice to lack MeCP2 in small populations of neurons in the hypothalamus, a command center of the brain that controls several physiological states.

When they eliminated the MeCP2 protein from one specific group of neurons in the hypothalamus, the animals showed one feature of Rett syndrome: increased levels of a stress hormone in response to stress. The animals also became aggressive when they were put into a novel situation.

"That meant that the few neurons that lacked MeCP2 govern this behavior," she said. "It also suggested that we need this protein to temper the response of our neurons so we behave appropriately when we experience a new social setting."

People with autism frequently get frustrated in novel situations, she said. A colleague in Germany reported seeing aggression in patients with milder Rett Syndrome.

"The other thing that surprised us was that the animals gained weight and kept on getting more obese as they got older," she said. "They ate unstoppably. In the absence of MeCP2, the signals that work within the hypothalamus to tell us we are full and need to stop eating are in part regulated by this protein. Without MeCP2, the neurons don't get the signal and you keep eating. It reveals a function of the protein not suspected before," she said.

The study also demonstrates that this technique – knocking out essential proteins in small populations of cells in the brain – could help reveal which neurons are important for which behaviors.

In the future, Zoghbi and her colleagues plan to study the function of MeCP2 in other neurons using the same technique.

Source: Baylor College of Medicine

Related stories:

The Rett gene -- a rogue activator
In 1999, when Dr. Huda Zoghbi and her Baylor College of Medicine colleagues identified a mutation of the gene MeCP2 as the culprit in Rett syndrome, a neurodevelopmental disorder, the discovery was only the prelude to understanding a symphony of neurological missteps.
Brain needs perfection in synapse number
Like Goldilocks, the brain seeks proportions that are just right. The proper number of synapses or communication between nerve cells, determined early in life, is crucial to having a healthy brain that can learn and retain information.
How Rett Syndrome mutation targets the brain
Researchers have pinpointed why mutations that cause Rett Syndrome (RTT)--among the leading causes of mental retardation in females--specifically target the brain rather than other body tissues. They said their findings yield important insight into the origin and course of the disease.
Research on understanding DNA segregation earns top award for young life scientists
For his research of DNA segregation, assembly and regulation of bacterial actin-like proteins, and cytoskeleton, Ethan Clark Garner, a regional winner from North America, has been named the Grand Prize winner for the GE & Science Prize for Young Life Scientists. The competition, which includes a grand-prize award of $25,000, is supported by GE Healthcare and the journal Science, which is published by AAAS, the nonprofit science society.
Study sheds light on causes of HIV dementia
A new study led by researchers at Albert Einstein College of Medicine of Yeshiva University has clarified how two major variants of HIV differ in their ability to cause neurologic complications. The finding, published in Journal of Neuroscience, highlights a new target for drugs that could prevent HIV-associated dementia, an incurable and increasingly common complication in people with AIDS. Even with anti-retroviral drug therapies, up to one-half of people infected with HIV will develop mild to moderate neurological complications, according to some estimates.
Claudin 11 stops the leaks in neuronal myelin sheaths
Devaux and Gow demonstrate how a tight junction protein called claudin 11 makes the neuronal myelin sheath a snug fit. The study will be published in the December 1, 2008 issue of the Journal of Cell Biology.
Fruit fly discovery generates buzz about brain-damaging disorder in children
Johns Hopkins researchers have used fruit flies to gain new insights into a brain-damaging disorder afflicting children. Their work suggests a possible therapy for the disease, for which there is currently no treatment.
Molecule shuts down food intake and turns on 'siesta mode'
Researchers have identified a molecule that tells your brain your stomach is full – signaling that it's time to say no to a second piece of pumpkin pie and push back from the Thanksgiving table.

News discussion:

Medicine & Health news