Tsai's team also probed the biochemical mechanism by which environmental enrichment worked its magic, tracing it to proteins called histones, the spools that DNA winds around to create complexes called chromatin in the nuclei of cells. A process called acetylation, where a chemical group is added to histones, causes the protein structures to unravel, exposing parts of DNA, which may have only been accessible during development. This action can result in the activation of genes that had been switched off, and could be the cause of the recovery of synaptic strength. When the researchers administered drugs called histone deacetylase inhibitors (HDACs)—which promote acetylation—to mice, they had the same effect as environmental stimulation.
Tsai says her team wants to probe this biological mechanism further to find the actual targets of HDACs. "We want to know which are the most important genes that are responsible for the improved learning and recovery of memories," she adds. This way, more specific therapeutics can be tailored to activate the correct proteins to counter the effects of neuronal loss. "I really hope,'' she says, "that our studies will one day translate into helping human patients with dementia."