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Licensed Unlicensed Requires Authentication Published by De Gruyter May 16, 2018

Metabolic regulation of synaptic activity

Sergei V. Fedorovich EMAIL logo and Tatyana V. Waseem


Brain tissue is bioenergetically expensive. In humans, it composes approximately 2% of body weight and accounts for approximately 20% of calorie consumption. The brain consumes energy mostly for ion and neurotransmitter transport, a process that occurs primarily in synapses. Therefore, synapses are expensive for any living creature who has brain. In many brain diseases, synapses are damaged earlier than neurons start dying. Synapses may be considered as vulnerable sites on a neuron. Ischemic stroke, an acute disturbance of blood flow in the brain, is an example of a metabolic disease that affects synapses. The associated excessive glutamate release, called excitotoxicity, is involved in neuronal death in brain ischemia. Another example of a metabolic disease is hypoglycemia, a complication of diabetes mellitus, which leads to neuronal death and brain dysfunction. However, synapse function can be corrected with “bioenergetic medicine”. In this review, a ketogenic diet is discussed as a curative option. In support of a ketogenic diet, whereby carbohydrates are replaced for fats in daily meals, epileptic seizures can be terminated. In this review, we discuss possible metabolic sensors in synapses. These may include molecules that perceive changes in composition of extracellular space, for instance, ketone body and lactate receptors, or molecules reacting to changes in cytosol, for instance, KATP channels or AMP kinase. Inhibition of endocytosis is believed to be a universal synaptic mechanism of adaptation to metabolic changes.


This work was supported by the Bielorussian Republican Foundation of Basic Investigation (grant no. B17-006). We thank Ms. Polina Voronina for helping with figure design. Funding agencies were not involved in the study design, collection, analysis and interpretation of data, report preparation, and decision to submit the article for publication.


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Received: 2017-10-30
Accepted: 2018-03-16
Published Online: 2018-05-16
Published in Print: 2018-11-27

©2018 Walter de Gruyter GmbH, Berlin/Boston

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