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Neurodegenerative disorders

HDAC2 is the one

Nature Reviews Drug Discovery volume 8, pages 538–539 (2009)Cite this article

The authors generated mice that overexpressed either HDAC1 or HDAC2 specifically in neurons. In Pavlovian fear conditioning tests mice that overexpressed HDAC2 showed impaired associative learning compared with wild-type (WT) mice, whereas HDAC1-overexpressing mice did not differ from WT mice. HDAC2-overexpressing mice also performed worse than WT and HDAC1-overexpressing mice in tests of spatial learning and spatial working memory. Conversely, HDAC2-deficient mice showed the opposite behavioural phenotype.

As synaptic plasticity is assumed to underlie learning and memory, the authors next investigated whether HDAC2 regulates this process. They found that HDAC2-overexpressing, but not HDAC1-overexpressing, mice had lower dendritic spine density and fewer synapses in the hippocampus than WT mice. HDAC2-deficient mice showed the opposite pattern. Moreover, levels of synaptophysin, a marker for presynaptic terminals, in the CA1 and the amygdala were lower than normal in HDAC2 overexpressors and higher than normal in HDAC2-deficient mice. In addition, high frequency stimulation-induced long-term potentiation in CA1 neurons was impaired in HDAC2 overexpressors and increased in HDAC2-deficient mice. This suggests that HDAC2 negatively regulates synapse formation and synaptic plasticity.

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References

ORIGINAL RESEARCH PAPER

  1. Guan, J.-S. et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459, 55–60 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

FURTHER READING

  1. Kazantsev, A. G. & Thompson, L. M. Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nature Rev. Drug Discov. 7, 854–868 (2008)

    Article  CAS  Google Scholar 

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  1. Nature Reviews Neuroscience,

    Leonie Welberg

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  1. Leonie Welberg
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Welberg, L. HDAC2 is the one. Nat Rev Drug Discov 8, 538–539 (2009). https://doi.org/10.1038/nrd2934

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  • DOI: https://doi.org/10.1038/nrd2934

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