Metabolic Flexibility in Astroglia and Its Impact on Neuronal Function

Abstract

This study analyzes metabolic differences in mitochondrial respiration and glycolysis between neurons and astrocytes. Primary cultures of both cell types were assessed using the Seahorse XFe24 bioenergetic analyser with the Mito Stress, Fuel Flex, and Glycolysis Stress tests. The results show that neurons have a 216% higher basal respiration than astrocytes, allocating 82.5% to ATP production, compared to 61% in astrocytes. Although proton leak in absolute values is similar, in relative terms it represents 17.5% in neurons and 39% in astrocytes. Furthermore, it was observed that both cell types depend mainly on fatty acid oxidation, although astrocytes also use glutamine (12.09%) and glucose (11.83%), while neurons rely almost exclusively on fatty acids. Finally, astrocytes showed a basal glycolytic rate and glycolytic reserve 79.1% and 116% higher than those of neurons. These findings demonstrate how neurons are highly specialized in maximizing ATP production via oxidative phosphorylation, whereas astrocytes display a more flexible metabolism, adapted to support and signaling functions which are essential to the function of the central nervous system.

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Agilent.com [internet]. Santa Clara: Agilent Technologies, Inc.; 2024 [citado 13 de jul de 2025]. How Agilent Seahorse XF Analyzers Work. Disponible en www.agilent.com

Delgado-Esteban M, García-Higuera I, Maestre C, Moreno S, Almeida A. APC/C-Cdh1 coordinates neurogenesis and cortical size during development. Nat Commun. 2013;4(1):2879.

Ioannou MS, Jackson J, Sheu SH, Chang CL, Weigel AV, Liu H, Passoli HA, Xu CS, Pang S, Matthies D, Hess HF, Lippincott-Schwartz J, Liu Z. Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity. Cell. 2019;177(6):1522-1535.e14.

Jimenez-Blasco D, Agulla J, Lapresa R, Garcia-Macia M, Bobo-Jimenez V, Garcia-Rodriguez D, Manjarres-Raza I, Fernandez E, Jeanson Y, Khoury S, Portais JC, Padro D, Ramos-Cabrer P, Carmeliet P, Almeida A, Bolaños JP. Weak neuronal glycolysis sustains cognition and organismal fitness. Nat Metab. 2024;6(7):1253-67.

Lopez-Fabuel I, L Douce J, Logan A, James AM, Bonvento G, Murphy MP, Almeida A, Bolaños JP. Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes. Proc Natl Acad Sci U S A. 2016;113(46):13063-8.

Turner DA, Adamson DC. Neuronal-astrocyte metabolic interactions: understanding the transition into abnormal astrocytoma metabolism. J Neuropathol Exp Neurol. 2011;70(3):167-76.

Vicente-Gutierrez C, Bonora N, Bobo-Jimenez V, Jimenez-Blasco D, Lopez-Fabuel I, Fernandez E, Josephine C, Bonvento G, Enriquez JA, Almeida A, Bolaños JP. Astrocytic mitochondrial ROS modulate brain metabolism and mouse behaviour. Nat Metab. 2019;1(2):201-11.
Nicolás Zapata, G., Delgado Esteban, M., & Bolaños, J. P. (2025). Metabolic Flexibility in Astroglia and Its Impact on Neuronal Function. FarmaJournal, 10(2), 77–86. https://doi.org/10.14201/fj20251027786

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Author Biography

Juan P. Bolaños

,
Universidad de Salamanca

 

 

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