Down memory lane
A. Fischer et al., “Recovery of learning and memory is associated with chromatin remodeling,” Nature, 447:178–82, 2007. (Cited in 82 papers)
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 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.
Tsai’s team showed that increased neuronal levels of HDAC2, but not HDAC1, are related...
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:|
|Neurodegenerative mice with enrichment:||38%|
|Neurodegenerative mice with HDAC inhibitor:||45%|