Neuroglia and brain energy metabolism

The glial control of energy homeostasis is of crucial importance for health and disease. Astrocytes in particular play a major role in controlling the equilibrium among adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP), and adenosine. Any energy crisis leads to a drop in ATP, and the resulting increase in adenosine is an evolutionary ancient mechanism to suppress energy-consuming activities. The maintenance of brain energy homeostasis, in turn, requires the availability of energy sources, such as glucose and ketones. Astrocytes have assumed an important role in enabling efficient energy utilization by neurons. In addition, neurons are under the metabolic control of astrocytes through regulation of glutamate and GABA levels. The intricate interplay between glial brain energy metabolism and brain function can be best understood once the homeostatic system of energy metabolism is brought out of control. This has best been studied within the context of epilepsy where metabolic treatments provide unprecedented opportunities for the control of seizures that are refractory to conventional antiseizure medications. This chapter will discuss astroglial energy metabolism in the healthy brain and will use epilepsy as a model condition in which glial brain energy homeostasis is disrupted. We will conclude with an outlook on how those principles can be applied to other conditions such as Alzheimer disease.