More likely, the results picque the interest of neuroscientists, but there is much already known about HDAC inhibitors in the learning models, and the finding is unlikely to yield more than candidates with more powerful impact on learning than the extant HDAC inhibitors, including Valproate, or Depakote, which is used in neuroscience paradigms for its HDAC inhibitory effect. Check out the following abstract:
[RESEARCH] Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear
Thursday, April 05, 2007, 6:00:00 PM | Bredy, T. W., Wu, H., Crego, C., Zellhoefer, J., Sun, Y. E., Barad, M.
Extinction of conditioned fear is an important model both of inhibitory learning and of behavior therapy for human anxiety disorders. Like other forms of learning, extinction learning is long-lasting and depends on regulated gene expression. Epigenetic mechanisms make an important contribution to persistent changes in gene expression; therefore, in these studies, we have investigated whether epigenetic regulation of gene expression contributes to fear extinction. Since brain-derived neurotrophic factor (BDNF) is crucial for synaptic plasticity and for the maintenance of long-term memory, we examined histone modifications around two BDNF gene promoters after extinction of cued fear, as potential targets of learning-induced epigenetic regulation of gene expression. Valproic acid (VPA), used for some time as an anticonvulsant and a mood stabilizer, modulates the expression of BDNF, and is a histone deacetylase (HDAC) inhibitor. Here, we report that extinction of conditioned fear is accompanied by a significant increase in histone H4 acetylation around the BDNF P4 gene promoter and increases in BDNF exon I and IV mRNA expression in prefrontal cortex, that VPA enhances long-term memory for extinction because of its HDAC inhibitor effects, and that VPA potentiates the effect of weak extinction training on histone H4 acetylation around both the BDNF P1 and P4 gene promoters and on BDNF exon IV mRNA expression. These results suggest a relationship between histone H4 modification, epigenetic regulation of BDNF gene expression, and long-term memory for extinction of conditioned fear. In addition, they suggest that HDAC inhibitors may become a useful pharmacological adjunct to psychotherapy for human anxiety disorders.
Valproate is already used in the therapeutic mix of drugs for a variety of problems associated with Alzheimer's (mostly for the mood stabilizing effects) and I have yet to see any science published on any remarkable improvement in memory or adaptive function for these patients even though the drug can have its intended clinical impact.
If the researchers can find another, more powerful HDAC inhibitor, it might help with the clinical picture for Alzheimer's disease, but might also mimic the acetylcholinesterase inhibitors (like aricept) already being used.
JM2C,
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