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Availability of neurotransmitter glutamate is diminished when β‐hydroxybutyrate replaces glucose in cultured neurons
Author(s) -
Lund Trine M,
Risa Øystein,
Sonnewald Ursula,
Schousboe Arne,
Waagepetersen Helle S
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06115.x
Subject(s) - glutamate receptor , neurotransmitter , neuroscience , neurotransmitter systems , chemistry , biochemistry , biology , central nervous system , dopamine , receptor
Abstract Ketone bodies serve as alternative energy substrates for the brain in cases of low glucose availability such as during starvation or in patients treated with a ketogenic diet. The ketone bodies are metabolized via a distinct pathway confined to the mitochondria. We have compared metabolism of [2,4‐ 13 C]β‐hydroxybutyrate to that of [1,6‐ 13 C]glucose in cultured glutamatergic neurons and investigated the effect of neuronal activity focusing on the aspartate–glutamate homeostasis, an essential component of the excitatory activity in the brain. The amount of 13 C incorporation and cellular content was lower for glutamate and higher for aspartate in the presence of [2,4‐ 13 C]β‐hydroxybutyrate as opposed to [1,6‐ 13 C]glucose. Our results suggest that the change in aspartate–glutamate homeostasis is due to a decreased availability of NADH for cytosolic malate dehydrogenase and thus reduced malate–aspartate shuttle activity in neurons using β‐hydroxybutyrate. In the presence of glucose, the glutamate content decreased significantly upon activation of neurotransmitter release, whereas in the presence of only β‐hydroxybutyrate, no decrease in the glutamate content was observed. Thus, the fraction of the glutamate pool available for transmitter release was diminished when metabolizing β‐hydroxybutyrate, which is in line with the hypothesis of formation of transmitter glutamate via an obligatory involvement of the malate–aspartate shuttle.