Cancer Drug Induces HDAC Inhibitor and Enhance Long-term Memory

by Medindia Content Team on  June 6, 2007 at 4:18 PM Drug News   - G J E 4
Cancer Drug Induces HDAC Inhibitor and Enhance Long-term Memory
University of California scientists have found that cancer drug enhances long-term memory and strengthen neural connections in the brain.

A protein complex called chromatin causes genomic DNA to compress much like a telephone cord shortens as it coils. When chromatin loosens, genes associated with memory can activate more easily. Previous studies have shown that the protein CBP causes chromatin to relax, thus facilitating gene activation required for memory formation. The enzymes that reverse this process, or make the chromatin tighter, are known as HDACs. UCI scientists found in this study that HDAC inhibitors loosen chromatin and lead to stronger memory formation.

"This is a fundamental aspect of molecular biology, and it is fascinating that it can impact memory, cancer and neurodegeneration - and potentially other conditions such as drug addiction and other psychiatric disorders," said Marcelo Wood, assistant professor in the Department of Neurobiology ."

Wood and his colleagues placed mice in a chamber and gave them mild electric shocks, Afterward, scientists injected HDAC inhibitors into the brains of mice, targeting the hippocampus, a region involved in short-term and long-term memory. A day later, the scientists returned the mice to the chamber to see how well they remembered the place in which they received the shock.

Mice treated with HDAC inhibitors froze in place significantly longer than those that did not receive the drug, indicating that the treated mice formed stronger memories of the chamber than the untreated mice. The scientists also examined brain tissue and found that neural connections in the hippocampus were stronger in the samples treated with HDAC inhibitors.

"After an event, a critical window exists when memory consolidation is occurring. During that time, genes associated with memory need to be turned on for certain types of long-term memory to be formed," Wood said. "For the HDAC inhibitor to enhance memory, we need to administer the drug during this critical period when gene expression is required.",he added.

Wood and his colleagues discovered that the protein CBP must be present for HDAC inhibitors to improve memory,When tested in mice genetically engineered without CBP, the HDAC inhibitors did not improve memory. When CBP is blocked in humans, it can lead to neurodegeneration associated with Huntington's disease and cognitive deficits in Rubenstein-Taybi syndrome. HDAC inhibitors may help overcome that blockage and lead to better neural function in people with those disorders - and perhaps improve memory as well.

Source: Eurekalert

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