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Synaptic energy metabolism and neuronal excitability, in sickness and health
Author(s) -
Oyarzabal Alfonso,
MarinValencia Isaac
Publication year - 2019
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1002/jimd.12071
Subject(s) - neurotransmission , neuroscience , epilepsy , biology , synaptic cleft , energy metabolism , synaptic fatigue , carbohydrate metabolism , synaptic plasticity , excitatory postsynaptic potential , central nervous system , neurotransmitter , inhibitory postsynaptic potential , biochemistry , endocrinology , receptor
Most of the energy produced in the brain is dedicated to supporting synaptic transmission. Glucose is the main fuel, providing energy and carbon skeletons to the cells that execute and support synaptic function: neurons and astrocytes, respectively. It is unclear, however, how glucose is provided to and used by these cells under different levels of synaptic activity. It is even more unclear how diseases that impair glucose uptake and oxidation in the brain alter metabolism in neurons and astrocytes, disrupt synaptic activity, and cause neurological dysfunction, of which seizures are one of the most common clinical manifestations. Poor mechanistic understanding of diseases involving synaptic energy metabolism has prevented the expansion of therapeutic options, which, in most cases, are limited to symptomatic treatments. To shed light on the intersections between metabolism, synaptic transmission, and neuronal excitability, we briefly review current knowledge of compartmentalized metabolism in neurons and astrocytes, the biochemical pathways that fuel synaptic transmission at resting and active states, and the mechanisms by which disorders of brain glucose metabolism disrupt neuronal excitability and synaptic function and cause neurological disease in the form of epilepsy.