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OHSU Researchers Discover Brain Cell Mechanism Possibly Linked to Mental Retardation

   Portland, Ore.

Discovery involves development of mouse model that may provide new target for drugs and other therapeutics

Researchers at Oregon Health & Science University (OHSU) have discovered a key cellular mechanism in the brain possibly involved in mental retardation. The research may be used to develop new drugs or therapies to combat the condition. The research, which was conducted in mice, also may provide scientists with an animal model for mental retardation that will be of use in future studies aimed at understanding and treating the human condition.

The research, which is printed in the Feb. 18 edition of the journal Proceedings of the National Academy of Sciences, centers on a key protein called WAVE-1 that is found throughout the brain. Researchers at OHSU produced mice lacking the WAVE-1 protein. Following observation, these animals were found to have balance, motor, learning and memory deficits. These symptoms correlate with one form of mental retardation found in humans.

"WAVE-1 is a very important protein involved in brain cell communication," said researcher John Scott, Ph.D., an associate investigator of the Howard Hughes Medical Institute and a senior scientist in the OHSU Vollum Institute. "The protein acts like a scaffolding that supports the lines of communication between different parts of the cell."

Scott and other OHSU researchers believe the absence of the WAVE-1 protein causes a partial breakdown of the brain cell communication system, which results in reduced learning ability and other effects associated with mental retardation. While there are thought to be literally hundreds of causes for mental retardation, it's believed the breakdown of important cellular communication systems is involved in many, if not all, forms.

One major conclusion of the research is that mental retardation involves many more areas of the brain than first expected.

"The protein is found in a variety of regions of the brain, including the hippocampus and the cerebellum," explained Jacob Raber, Ph.D., an assistant professor of behavioral neuroscience and neurology in the OHSU School of Medicine. "Through studying mouse models, we hope to further understand and describe the roles of various brain regions in the important functions impaired by mental retardation."

The Raber lab's involvement in the project is a unique partnership between behavioral neuroscience and biochemistry experts.

"The Raber lab is literally across the hall from our lab," explained Scott. "The close proximity resulted in numerous conversations between the two labs and, finally, collaboration on this project."

Scott Soderling, Ph.D., a lead researcher on this project, also noted an unexpected trait found in mice lacking the WAVE-1 protein - reduced anxiety. Future studies conducted between the Scott and Raber labs will try to determine whether this trait is also found in humans with the corresponding form of mental retardation.

This research was sponsored by Howard Hughes Medical Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, a component of the National Institutes of Health.

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