Glucose-derived glutamate drives neuronal terminal differentiation in vitro.

Autor:	D'Andrea L; Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Via Giuseppe Balzaretti 9, 20133, Milan, Italy., Audano M; Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Via Giuseppe Balzaretti 9, 20133, Milan, Italy., Pedretti S; Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Via Giuseppe Balzaretti 9, 20133, Milan, Italy., Pelucchi S; Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Via Giuseppe Balzaretti 9, 20133, Milan, Italy., Stringhi R; Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Via Giuseppe Balzaretti 9, 20133, Milan, Italy., Imperato G; Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Via Giuseppe Balzaretti 9, 20133, Milan, Italy., De Cesare G; Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Via Giuseppe Balzaretti 9, 20133, Milan, Italy., Cambria C; Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Via F.lli Cervi 93, Segrate, 20054 Milan and via Vanvitelli 32, Milan, Italy., Laporte MH; Department of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland., Zamboni N; Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland., Antonucci F; Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Via F.lli Cervi 93, Segrate, 20054 Milan and via Vanvitelli 32, Milan, Italy.; Institute of Neuroscience, IN-CNR, Milan, Italy., Di Luca M; Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Via Giuseppe Balzaretti 9, 20133, Milan, Italy., Mitro N; Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Via Giuseppe Balzaretti 9, 20133, Milan, Italy. nico.mitro@unimi.it.; Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy. nico.mitro@unimi.it., Marcello E; Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Via Giuseppe Balzaretti 9, 20133, Milan, Italy. elena.marcello@unimi.it.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2024 Mar; Vol. 25 (3), pp. 991-1021. Date of Electronic Publication: 2024 Jan 19.
DOI:	10.1038/s44319-023-00048-8
Abstrakt:	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 reveals 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 in mitochondrial pyruvate transporter-inhibited cells. Furthermore, the selective activation of metabotropic glutamate receptors restores the impairment of neuronal differentiation due to the reduced generation of glucose-derived glutamate and rescues synaptic local translation. Fatty acid oxidation does not impact neuronal maturation. Whereas glutamine metabolism is important for mitochondria, it is not for endogenous glutamate production. Our results provide insights into the role of glucose-derived glutamate as a key player in neuronal terminal differentiation. (© 2024. The Author(s).)
Databáze:	MEDLINE
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