Could Poor Sleep and Histone Modification Degrade Your Memory?

Impaired sleep is a common issue that plagues many people. Not getting enough rest can lead to moodiness, cognitive decline, increased anxiety, and difficulty concentrating or remembering things. It’s estimated that 50-70 million adults in the US have sleep or wakefulness disorder, according to the CDC. But, for something so crucial to our lives, sleep is still shrouded in mystery. Interestingly, previous research has uncovered a link between sleep disorders and memory. Other studies have even shown that short-term sleep loss can alter DNA methylation of “clock” genes and just one night without sleep can adjust metabolism and lead to weight gain. However, the exact molecular mechanisms underlying the interplay between sleep disorders and cognitive ability are not yet known.

Researchers from Tianjin Institute of Health and Environmental Medicine set out to elucidate the epigenetic influence that histone acetylation – a common epigenetic mechanism – has on impaired memory as a result of lack of sleep. Other studies have demonstrated a connection between epigenetic marks and hippocampal learning and memory. For instance, histone deacetylases (HDACs), particularly HDAC2, have been implicated in memory formation. HDACs are enzymes that reverse histone acetylation, the process by which acetyl groups are added to histones. This plays a part in chromatin remodeling, specifically relaxing the chromatin structure and increasing gene expression.

In their study, published in Neurochemical Research, the group of researchers investigated post-translation modification of histones in the hippocampus of male rats that were suffering from sleep deprivation. They also conducted a spatial learning and memory task to assess the cognitive decline associated with lack of sleep.

After three days of sleep deprivation, the rats displayed spatial memory impairment. The researchers found that this was associated with decreased histone acetylation levels, increased histone deacetylase 2 (HDAC2) expression, and decreased histone acetyltransferase (CBP) expression. Furthermore, histone H3 and H4 acetylation levels were significantly reduced in the promoters of bdnf, or brain-derived neurotrophic factor. This protein is highly implicated in memory formation and crucially involved in the creation of synapses between neurons, or synaptogenesis, and synaptic plasticity.

In order to more clearly understand the role of histone modification in the bdnf promoter region, the researchers carried out a ChIP assay using EpiGentek’s EpiQuik Chromatin Immunoprecipitation (ChIP) Kit. This kit can be used for immunoprecipitating chromatin specifically from cells in a microplate format. The team reported that the ChIP, followed by qPCR, “revealed marked reductions in H3K9 and H4K12 acetylation levels in the multiple bdnf promoter IV regions of hippocampal tissues from sleep-deprived rats.” They concluded that sleep deprivation can downregulate BDNF expression and the BDNF signaling pathway due to decreased histone H3 and H4 acetylation levels in the promoter regions of bdnf. This could be interfering with the process of making and storing new memories, which is thought to occur while we sleep.

The team also assessed the effects of an HDAC inhibitor, trichostatin A (TSA), on the sleep-deprived rats. They found that administering the HDAC inhibitor reversed this process and restored spatial memory function to the sleep-deprived rats. The researchers believe that HDAC inhibition could “confer protection against [sleep deprivation]-induced impairment in spatial memory and hippocampal functions.”

This new information gives us clues to the epigenetic mechanisms underlying sleep deprivation and its effects on cognitive function and memory. It further supports the importance being well-rested has on our daily lives. With new research, we can begin to understand all important facets of sleep and perhaps even develop therapies or preventative strategies for reducing the negative effects we experience as a result of not getting enough of it.

Source: Duan R, Liu X, Wang T, Wu L, Gao X, Zhang Z. (2016). Histone Acetylation Regulation in Sleep Deprivation-Induced Spatial Memory Impairment. Neurochem Res. 41(9):2223-32.