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Target of Inhibitors of Memory Loss Identified

Last Updated: May 08, 2009.

One member of the histone deacetylase family, which represses gene expression, has been identified as a negative regulator of learning and memory and can be targeted by inhibitors leading to enhanced learning and memory, according to a study in the May 7 issue of Nature.

FRIDAY, May 8 (HealthDay News) -- One member of the histone deacetylase (HDAC) family, which represses gene expression, has been identified as a negative regulator of learning and memory and can be targeted by inhibitors leading to enhanced learning and memory, according to a study in the May 7 issue of Nature.

Noting that previous studies have suggested that HDAC inhibitors enhance learning and memory even after massive neuronal loss in mice, Ji-Song Guan, Ph.D., from the Massachusetts Institute of Technology in Cambridge, and colleagues investigated which HDAC family members were important in learning and memory using selective inhibitors and by overexpressing and deleting the genes.

The researchers found that HDAC2, but not HDAC1, was important in negatively regulating dendritic spine density, synapse number, synaptic plasticity, and memory formation. Synapse number and memory improved after treating mice overexpressing HDAC2 with HDAC2 inhibitors, but not HDAC2-deficient mice. HDAC2 was present in the promoter regions of genes implicated in synaptic plasticity and memory formation, according to the authors.

"Taken together, our results suggest that HDAC2 functions in modulating synaptic plasticity and long-lasting changes of neural circuits, which in turn negatively regulates learning and memory," Guan and colleagues conclude. "These observations encourage the development and testing of HDAC2-selective inhibitors for human diseases associated with memory impairment."

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