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| http://dx.doi.org/10.1073/pnas.1619813114 | DOI Listing |
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Lactate: Beyond a mere fuel in the epileptic brain.
Neuropharmacology
March 2025
Department of Pharmacology, Medical School of Southeast University, Nanjing, China. Electronic address:
Epilepsy, a prevalent neurological disorder characterized by spontaneous recurrent seizures, significantly impacts physiological and cognitive functions. Emerging evidence suggests a crucial role for metabolic factors, particularly lactate, in epilepsy. We discuss the applicability of the astrocyte-neuron lactate shuttle (ANLS) model during acute seizure events and examine lactate's metabolic adaptation in epilepsy progression.
View Article and Find Full Text PDFATP Restoration by ATP-Deprived Cultured Primary Astrocytes.
Neurochem Res
November 2024
Centre for Biomolecular Interactions Bremen Faculty 2 (Biology/Chemistry), University of Bremen, P.O. Box 330440, 28334, Bremen, Germany.
A high cellular concentration of adenosine triphosphate (ATP) is essential to fuel many important functions of brain astrocytes. Although cellular ATP depletion has frequently been reported for astrocytes, little is known on the metabolic pathways that contribute to ATP restoration by ATP-depleted astrocytes. Incubation of cultured primary rat astrocytes in glucose-free buffer for 60 min with the mitochondrial uncoupler BAM15 lowered the cellular ATP content by around 70%, the total amount of adenosine phosphates by around 50% and the adenylate energy charge (AEC) from 0.
View Article and Find Full Text PDFBrain Metabolism in Health and Neurodegeneration: The Interplay Among Neurons and Astrocytes.
Cells
October 2024
Blue Brain Project, École Polytechnique Fédérale de Lausanne, 1202 Geneva, Switzerland.
The regulation of energy in the brain has garnered substantial attention in recent years due to its significant implications in various disorders and aging. The brain's energy metabolism is a dynamic and tightly regulated network that balances energy demand and supply by engaging complementary molecular pathways. The crosstalk among these pathways enables the system to switch its preferred fuel source based on substrate availability, activity levels, and cell state-related factors such as redox balance.
View Article and Find Full Text PDFMetabolic preferences of astrocytes: Functional metabolic mapping reveals butyrate outcompetes acetate.
J Cereb Blood Flow Metab
September 2024
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Disruptions to the gut-brain-axis have been linked to neurodegenerative disorders. Of these disruptions, reductions in the levels of short-chain fatty acids (SCFAs), like butyrate, have been observed in mouse models of Alzheimer's disease (AD). Butyrate supplementation in mice has shown promise in reducing neuroinflammation, amyloid-β accumulation, and enhancing memory.
View Article and Find Full Text PDFInhibition of the mitochondrial pyruvate carrier in astrocytes reduces amyloid and tau accumulation in the 3xTgAD mouse model of Alzheimer's disease.
Neurobiol Dis
October 2024
Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Department of Psychiatry, University Hospital of Geneva and Geneva Neuroscience Center, Geneva, Switzerland. Electronic address:
Alzheimer's Disease (AD) is characterized by an accumulation of pathologic amyloid-beta (Aβ) and Tau proteins, neuroinflammation, metabolic changes and neuronal death. Reactive astrocytes participate in these pathophysiological processes by releasing pro-inflammatory molecules and recruiting the immune system, which further reinforces inflammation and contributes to neuronal death. Besides these neurotoxic effects, astrocytes can protect neurons by providing them with high amounts of lactate as energy fuel.
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