Enzyme Linked to Long-Term Memory Disorder

A metabolic glitch might prevent the development of long-term memory in Angelman’s Syndrome, according to a Baylor College of Medicine study published in the April 1 issue of the Journal of Neuroscience.

Angelman’s Syndrome is a rare, genetic condition that causes mental retardation, a nearly total lack of speech and unique behaviors such as inappropriate bursts of laughter and hyperactivity. Using an Angelman’s Syndrome mouse model developed at Baylor, neuroscientists discovered that malfunction of the CaMKII enzyme disrupts the memory process.

“We have found a very specific deficit in the hippocampus of the brain in the Angelman’s mouse in terms of higher learning,” said David Sweatt, Ph.D., professor of neuroscience at Baylor and lead author of the study.

Located near the base of the brain, the hippocampus functions as its memory processor. Scientists hypothesize that memory is formed through a process called long-term potentiation, or LTP. LTP occurs when the strength of the connection between nerve cells changes. Sustained changes form memories.

To test these connections, Sweatt and his colleagues stimulated the brain tissue of the Angelman’s mice compared to a group of control mice. They found that the Angelman mice could not form sustained changes in nerve connections like the control group. Analyzing the tissue further, they found that it lacked normal activity of an enzyme called calcium/calmodulin-dependent protein kinase II, which regulates LTP.

The discovery gives researchers more information about what causes the rare, but profoundly disabling disease in humans.

“We are still missing the ‘black box’ that links the Angelman’s syndrome gene to the molecular and physiological changes that cause the disruption of the CaM kinase,” Sweatt said. “Trying to identify this link will be the next stage of our research.”

---

©2006 Texas Medical Center

---

E-Mail: tmcinfo@texmedctr.tmc.edu
URL: http://www.tmc.edu/tmcnews/04_15_03/page_04.html