A new study from the University of Birmingham, Alabama by Frankie Heyward et al. has presented the first evidence links hippocampus functions and epigenetic modifications, caused by obesity, to memory impairment.
Obesity, Neurobiology, and Epigenetics
Obesity is an epidemic that is currently plaguing developed nations around the world. 76 million people in America alone are obese, and obesity related diseases such as heart disease, type II diabetes, and certain cancers, are the leading cause of death. Furthermore, the average medical cost of obesity in America is over $100 billion per year . In addition to these diseases of the body, clinical studies have linked obesity to the higher risks for neurodegeneration and diseases of the mind. In particular, there have long since been correlations between obesity and memory impairment.
Indeed, studies with obesity induced rodents have shown spacial memory impairments related to hippocampus, abnormalities in hippocampal dendritic spine morphology, deficits in synaptic plasticity, and reduced dentate gyrus neurogenesis. Although there is no doubt that obesity can cause these impairments, there is currently no known molecular mechanism of disease.
However, a new study from the University of Birmingham, Alabama by Frankie Heyward et al. has presented the first evidence that epigenetic dysregulation may be the cause of this pathology. Specifically, altered methylation and hydroxymethylation patterns have been discovered in memory-related genes, most notably Sirt1, within the hippocampus of obese mice.
What is DNA Methylation?
One of the most important and well-studied types of epigenetic modification is DNA methylation or the addition of methyl (or in this case, also hydroxyethyl) groups to specific base pairs of DNA. Generally, increased levels of methylation of a gene cause decreased expression levels of that gene. This process is especially important because DNA methylation is often caused by environmental factors, such as lifestyles, toxins, and diets. Furthermore, DNA methylation has been shown to be hereditary, meaning that these modifications can persist within one’s own lifetime, and can even be inherited from parent to child.
The ability to remember events correctly is integral for deriving meaning from our lives. The hippocampus is the part of the brain that is responsible for forming memories, organizing memories, and storing memories. It is also is responsible for relating memories to sounds, sights, and smells that we encounter on a daily basis, and plays important roles in linearly organizing memories . It has also been implicated in emotional responses. Humans have two hippocampi, one located in each hemisphere of the brain. The hippocampus often shows signs of damage in diseases such as Alzheimer’s. Clearly, it is one of our most important organs, and its health should be of utmost priority .
Epigenetic Changes to Memory Function Can Be Brought On by Obesity
Because epigenetic regulation of memory has long been acknowledged, Heyward et al. sought to examine if there was a link between obesity related cognitive decline and epigenetic dysregulation. This question was assessed using a mouse model for obesity. Mice were fed either a high fat diet, or a control diet for 20 weeks, after which memory capabilities, as well as neural plasticity, were assessed.
As expected, mice fed the high fat diet were both more obese, and performed poorly in spatial memory and cognitive plasticity assays. The group then sought to measure the amount of methylation of known genes related to memory, which are both expressed in the hippocampus and expressed at lower levels in neurodegeneration associated with obesity.
What they found was that all of these genes contained hypermethylated promoter regions, meaning that the reason these genes are often underexpressed in obesity related memory problems could be because of epigenetic modifications. They then repeated the same assay in order to examine hydroxymethylation as well. Interestingly, they discovered that the only gene the exhibited higher levels of hydroxymethylation was sirc1, a gene which is important for memory consolidation
The group then sought to determine the kinetic relationship between obesity and these epigenetic modifications. In order to do this, they once again assessed methylation levels of memory related genes, but at different points in time throughout the life cycle of the mice. What they found was that these epigenetic changes weren’t present until about 16 weeks into the diet, even though the mice exhibited signs of obesity .
The implications of this study are vast. It has long since been known that out environments can alter the expression of our genes through epigenetic modifications. However, the extent and seriousness to which this can occur can often be underestimated. Obesity is a rising problem in America and all throughout the world. It is important to understand the many different ways that this epidemic, often one that plagues poorer communities, can deteriorate not only our bodies but also our minds.