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Down memory lane

By Elie Dolgin Down memory lane © Marc Phares / Photo Researchers, Inc The paper: A. Fischer et al., “Recovery of learning and memory is associated with chromatin remodeling,” Nature, 447:178–82, 2007. (Cited in 82 papers) The finding: Li-Huei Tsai and colleagues at the Massachusetts Institute of Technology showed that mentally stimulating environment caused chromatin modifications that restored learning and lo

Elie Dolgin

Down memory lane

© Marc Phares / Photo Researchers, Inc

The paper:

A. Fischer et al., “Recovery of learning and memory is associated with chromatin remodeling,” Nature, 447:178–82, 2007. (Cited in 82 papers)

The finding:

Li-Huei Tsai and colleagues at the Massachusetts Institute of Technology showed that mentally stimulating environment caused chromatin modifications that restored learning and long-term memory in a mouse model of severe neurodegeneration. Treatment with histone deacetylase (HDAC) inhibitors alone—which yielded less compact and more transcriptionally active chromatin—also led to a memory boost, even after significant brain atrophy and neuronal loss.

The impact:

The study “starts to shed some light on how HDAC inhibitors are enhancing synaptic plasticity of memory” by rewiring the brain to retrieve long-lost memories, says Marcelo Wood, a molecular neurobiologist at the University of California, Irvine.

The treatment:

Tsai’s team showed that increased neuronal levels of HDAC2, but not HDAC1, are related...

The future:

Tsai is collaborating with chemists at the Broad Institute’s Stanley Center for Psychiatric Research “to really help them to identify more selective HDAC2 inhibitors.” She then plans to validate any candidate compounds in her mouse models of neurodegenerative diseases. “That’s exactly where the field should be headed,” says Wood.

Freezing response to fear-induced memory test:
Wild-type mice: 44-46%
Neurodegenerative mice: 5-17%
Neurodegenerative mice with enrichment: 38%
Neurodegenerative mice with HDAC inhibitor: 45%

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