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Glucose-derived glutamate drives neuronal terminal differentiation in vitro


ABSTRACT: Neuronal maturation is the phase during which neurons acquire their final characteristics in terms of morphology, electrical activity, and metabolism. However, little is known about the metabolic pathways governing neuronal maturation. Here, we investigate the contribution of the main metabolic pathways, namely glucose, glutamine, and fatty acid oxidation, during the maturation of primary rat hippocampal neurons. Blunting glucose oxidation through the genetic and chemical inhibition of the mitochondrial pyruvate transporter revealed that this protein is critical for the production of glutamate, which is required for neuronal arborization, proper dendritic elongation, and spine formation. Glutamate supplementation in the early phase of differentiation restores morphological defects and synaptic function. Furthermore, the selective activation of metabotropic glutamate receptors fully restores the impairment of neuronal differentiation due to the reduced generation of glucose-derived glutamate by rescuing synaptic local translation. Fatty acid oxidation does not affect neuronal maturation. Whereas glutamine metabolism is important for mitochondria, but not for endogenous glutamate production. Our results provide new insights into the role of glucose-derived glutamate as a key player in neuronal terminal differentiation.

SUBMITTER: Dr. Laura D'Andrea 

PROVIDER: S-SCDT-10_1038-S44319-023-00048-8 | biostudies-other |

REPOSITORIES: biostudies-other

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