Study proves that “the administration of an anti-convulsive ketogenic diet is associated with gene regulating DNA methylation changes in rat TLE” (Kobow et al., 2013).

In epilepsy, it is shown that there is an increase, rather than a loss, of DNA methylation. The ketogenic diet (KD) is based on a high-fat and low-carbohydrate diet that acts as an anti-epileptic therapy.

It is recognized to work well in both humans and animal models, since it is well known that both, diet and environmental changes, play a very important role in the epigenome.  This diet was used by investigators, led by Katja Kobow, to examine methylation in the CpG islands of rats that are positive for temporal lobe epilepsy (TLE) (2013).  

In this study, the TLE rats were fed with a standard ketogenic diet, while strictly controlling body weight. Apart from the control group rats, the experimental group rats were prepared by inserting through brain surgery, a continuous video-electroencephalography monitor for studying of the brain before, during and after a seizure. DNA methylation profiling was made via examination of the extracted hippocampal tissue (2013). The investigators used Methyl-capture and massive parallel sequencing (Methyl-Seq) for analysis of this genomic DNA methylation. This was backed up by examination of mRNA (mRNA-Seq) sequencing from the same tissue.

The ketogenic diet was proven to regulate gene expression by modifying chromatin structure, by altering DNA methylation. Results showed that KD did not have a significant impact in the severity or duration of a clinical seizure, but it did however, affect the seizure frequency per week, by reducing those (2013). As mentioned before, epilepsy is related to hyper DNA methylation, but on the contrary, the KD diet was proven to “reduce DNA methylation at gene bodies as well as intronic and exonic regions.” (2013)

The KD, is “a well-recognized anti-epileptic treatment in children with severe and chronic epilepsy that delays chronification of the disease and partially rescues the DNA methylation and corresponding gene expression phenotype” (2013). This diet “interferes with aberrant seizure-related genomic and locus specific alterations in DNA methylation and gene expression” (2013). In this study, “both hyper- and hypomethylation events were detected with subsequent gene repression or activation” (2013).  It is not known exactly how the KD diet works to reduce DNA methylation and reduce the patient’s seizures. This study opens the doors for further epileptic analysis through epigenetics, in order to better understand and hopefully discover a new and better anti-seizure therapy.

References:

Kobow, K. et al. (2013) Deep sequencing reveals increased DNA methylation in chronic rat epilepsy. Acta Neuropathologica, 126(741-756). 

Access:

http://link.springer.com/article/10.1007/s00401-013-1168-8