Neurexin, neuroligin, glutamate
The autism genome project have been running scans on the whole of the human genome using gene chips:
The consortium leveraged the unprecedented statistical power generated by its unique sample set by using “gene chip” technology to look for genetic commonality in autistic individuals culled from almost 1,200 families. One third of the DNA and clinical data was provided by the Autism Genetic Resource Exchange (AGRE). The AGP also scanned DNA from these families for copy number variations (CNV), or sub-microscopic genomic insertions and deletions that scientists believe might be involved with this and other common diseases. The innovative combination of these two approaches implicates a previously unidentified region of chromosome 11, and neurexin 1, a member of a family of genes believed to be important in neuronal contact and communication, among other regions and genes in the genome. The neurexin finding in particular highlights a special group of neurons, called glutamate neurons, and the genes affecting their development and function, suggesting they play a critical role in autism spectrum disorders. AGP results
I’ve been searching for some kind of explanation of these findings, and Chris very kindly sent me this article last weekend:
DALLAS – Sept. 7, 2007 – Mice containing a mutated human gene implicated in autism exhibit the poor social skills but increased intelligence akin to the title character’s traits in the movie “Rain Man,” researchers at UT Southwestern Medical Center have found.
The researchers’ study also shows how the mutation affects nerve function and provides an animal model that might allow further study of the debilitating condition.
“It’s an attempt to replicate, as best we can, a complicated disease that has as a symptom an inability to use language effectively,” said Dr. Thomas Südhof, chairman of neuroscience and senior author of the study, which appears online in Science Express and will be published later in Science.
“Any model we make will only be an approximation of the human condition,” he cautioned.
Autism spectrum disorders cover a wide span of conditions and symptoms, from severe mental retardation to mild social impairment. In general, people with autism have problems with social interactions, such as maintaining eye contact or reading body language. They may also exhibit stereotypical behavior, such as being obsessed with lining up objects. In the movie “Rain Man,” the title character was unable to form social bonds and became distressed when his normal routine was disrupted, yet he could perform exceptional mental mathematics.
About 1.5 million people in the United States have autism spectrum disorders, with boys affected more often than girls.
Some cases of autism are genetically linked and have been associated with mutations that affect molecules called neuroligins, which link nerve cells together.
In the latest study, the researchers introduced a mutated human form of the neuroligin-3 molecule into mice. They then tested the animals’ social interactions by exposing them to an unknown mouse in a cage. The genetically engineered mice spent less time near the strange mouse than their normal littermates and preferred to spend time with inanimate objects.
The engineered mice were significantly better than normal, though, at learning a water maze, in which they had to find and learn the location of an underwater platform. They were also better at relearning a new position of the platform after it was moved.
“When you manipulate a brain, you usually don’t improve it,” Dr. Südhof said. “The fact that we get an improvement is very good. It shows we’re changing something specific; we’re affecting how the brain processes information.”
Other tests of coordination, anxiety and motor ability showed normal results, indicating that the changes in brain activity were specific, Dr. Südhof said.
The researchers also studied the patterns of electrical activity in the brain. Normally, some nerve cells halt, or inhibit, other nerve cells from firing, while others excite action in their neighbors. An imbalance in the normal pattern is thought to be involved in autism.
Nerve cells from the genetically engineered mice showed a significantly greater inhibitory action than their normal littermates, even though only about 10 percent of the normal amount of neuroligin-3 was present. This finding was a surprise, as other studies have indicated that a loss of inhibitory action might be involved in autism spectrum disorders, the researchers said.
The results indicate that focusing on inhibitory action might be a way to treat autistic behaviors, said Dr. Südhof, director of the Gill Center for Research on Brain Cell Communication and the C. Vincent Prothro Center for Research in Basic Neuroscience. He is a Howard Hughes Medical Institute investigator at UT Southwestern. ‘Rain Man’ mice provide model for autism
I’m surprised that researchers are surprised that there are inhibitory effects happening in autism! My brain feels like it’s in constant INHIBIT gear. My brain is always trying to tell me to stop talking and not make friends.