CNS metabolism Neuronal activity accounts for 80% of the brain’s energy consumption. Blood-borne glucose is an essential energy source for the adult human brain. Both neurons and astrocytes take up glucose via the cell-specific transporters GLUT1 and GLUT3. Upon increased demand neurons ability to take up glucose is limited and lactate provided by astrocytes becomes the primary oxidative fuel. Under certain conditions the brain can also utilize acetoacetate, b-hydroxybutyrate and acetone (ketone bodies) derived from fatty acids as alternative energy source. Neurons metabolize ketone bodies to Acetyl-CoA, which is further oxidized through the TCA cycle. High circulating levels of ketone bodies are known to protect the brain. Ketone bodies also prevent seizures in GLUT1 difficiency syndrome and are important for brain development, but cellular and molecular mechanisms underlying the protective effect of ketone bodies are not yet fully clear. In the following I discuss the presumable link of metabolism with epigenetic changes and implications in brain function.
Author Archives: wobokka
New epilepsy genes involved in epigenetics – a survey
A growing number of genes have been identified to be causative for genetic forms of epilepsy, which are neither ion channels, receptors nor other classical epilepsy genes but epigenetic players. The epigenetic enzymes and effector proteins described to be mutated in inherited genetic epilepsies as well as epileptic encephalopathies, intellectual disability syndromes and autism spectrum disorders with associated severe or occasional seizure phenotype are of various function. Since this function never seems to be sufficiently discussed in the respective publications and little is to be found on how these genes may be linked to the phenotype, here comes a little overview summarizing how epigenetics is contributing not only to symptomatic focal epilepsy but may also help to explain the phenotypic heterogeneity of genetic epilepsies.
Epigenetic signatures – profiling the epilepsies beyond genetics
What is epigenetics? In a single idea: the molecular memory of a cell. The system stores information of previously external (e.g. environmental) or internal (e.g. developmental) stimuli, learns from this experience and responds. A collection of specific tags tells genes whether to be ON or OFF. Hardcore epigeneticists claim that an epigenetic tag should be meiotically and/or mitotically heritable, self-perpetuating, and reversible. DNA methylation is the mechanism coming closest to this ideal. A more liberal definition not focusing on heritability refers to any structural adaptation of the chromatin template that regulates gene expression. This would also include posttranslational histone tail modifications, incorporation of histone variants, chromatin remodeling processes, and action of non-coding RNAs. The large variety, flexibility, interdependence and potential synergistic effects of epigenetic mechanisms could provide the molecular basis for any phenotypic variation in physiological and pathological conditions. In epilepsy research this is especially interesting with regard to the stimulus-driven activity and connectivity of post-mitotic neurons in the adult brain. We set out to study methylation for the most common form of epilepsy in adults. Continue reading
