This weeks Paper of the Week adds some detail to connections between cognitive function and epigenetics as histone modifications. The paper is "An epigenetic blockade of cognitive functions in the neurodegenerating brain" by Gräff, et al. The paper was published in Nature on 29 Feb 2012.
What makes this a noteworthy paper, in my opinion, is the link between Alzheimer disease and lifestyle choices. The lifestyle choices of smoking, diet and physical activity (and likely others) have the ability to affect epigenetic patterns of either DNA methylation or histone acetylation. The authors demonstrate that cognitive abilities in a brain with developing neurodegeneration are held in check by an epigenetic-based restriction of gene transcription, and this is potentially reversible. This repression of mRNA synthesis is mediated by histone deacetylase 2 (or HDAC2). Furthermore, this repression is increased by Alzheimer’s-disease-related neurotoxic insults in vitro, in two mouse models of neurodegeneration and in patients with Alzheimer’s disease.
Imagine if something in the diet or something like exercise could reduce or repress the built-up activity of HDAC2 that occurs as a result of the neurotoxic insults described in the paper. That would be exciting. Thus, I see this work as important in showing, again, how environment and epigenetics can affect disease state. It is certainly likely that certain lifestyle choices would have greater or lesser impact on neurodegenerative processes and either augment or enhance the genetic risk of disease. Although not demonstrated in this article, it could be that an APOE epsilon 4 (E4) genotype, with its increased risk of Alzheimer disease could be partially ameliorated via those lifestyle choices that inhibit or curtail excessive HDAC2 activity. That woud indeed be quite exciting.