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 to a reduction in synapse number, dendrite density, and learning ability in mice (Nature, 459:55–60, 2009). Future therapeutic agents could improve cognition in humans by targeting this particular enzyme, says Tsai.

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%

Many Processes Involve Chromatin Remodeling


?Recovery of learning and memory is associated with chromatin remodeling,?
LINK


There is evidence that modulation of chromatin modification can facilitate extinction and prevent reinstatement of induced behavioral changes.

Activating chromatin modifications increase the accessibility of the chromatin to RNA polymerase, where repressing modifications decrease the accessibility to RNA polymerase. The repressing modifications cause the gene to become inactivated. Once the repressing modifications are removed the activating modifications attract transcription machinery, and the gene becomes activated.

Several distinct classes of enzyme can modify histones at multiple sites. "Epigenetics" refers to changes in phenotype or gene expression caused without change in the gene's DNA compositional sequence. These changes may remain through cell divisions for the remainder of the cell's life and may also last for multiple generations.


The treatment and conclusions in "Recovery of learning and memory is associated with chromatin remodeling" reminds me of old Soviet joke about biology experiment, measuring frog response. Data in the log:

Day 1: Commanded frog to jump. Frog jumped 2 feet.
Day 2: Amputated one foreleg. On voice command, frog jumped 18 inches.
Day 3: Amputated other foreleg. On voice command, frog jumped 12 inches.
Day 4: Amputated one rear leg. On voice command, frog jumped 6 inches.
Day 5: Amputated second rear leg. On voice command, frog displays deafness.


Dov Henis
(Comments From The 22nd Century)
Updated Life's Manifest May 2009
LINK