Fluid Brain Glycolysis: Limits, Speed, Location, Moonlighting, and the Fates of Glycogen and Lactate

Barros, L. Felipe; Martín, Alejandro San; Ruminot, Iván; Sandoval, Pamela Y.; Baeza-Lehnert, Felipe; Arce-Molina, Robinson; Rauseo, Daniela; Contreras-Baeza, Yasna; Galaz, Alex; Valdivia, Sharin

doi:10.1007/s11064-020-03005-2

Cited by 14 publications

(15 citation statements)

References 77 publications

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“…After phosphorylation, G6P may form glycogen or enter the PPP (Figure 2). In addition, glycolysis is branching off and on at multiple points, likely suggesting that pyruvate is not made at the same rate that glucose is consumed, as elegantly reminded by Felipe Barros (Barros et al, 2020). As we already mentioned above, glycolytic intermediates are providing carbons to generate biomass (Lunt and Vander Heiden, 2011).…”

Section: Glucose Breakdown: Beyond Atp Productionmentioning

confidence: 89%

Astrocyte-neuron metabolic cooperation shapes brain activity

2021

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Section: Glucose Breakdown: Beyond Atp Productionmentioning

confidence: 89%

Astrocyte-neuron metabolic cooperation shapes brain activity

2021

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“…Lactate is a metabolic end-product that cannot directly be used and requires its conversion into pyruvate to serve as energy and carbon source to the tricarboxylic acid (TCA) cycle ( Barros et al, 2020 ). One of the advantages of producing lactate that is not readily consumed is to allow its distribution and exchanges between lactate producing and lactate consuming cells ( Brooks, 2018 ).…”

Section: Astrocyte-mediated Metabolic Supportmentioning

confidence: 99%

Astrocytes as Key Regulators of Brain Energy Metabolism: New Therapeutic Perspectives

et al. 2022

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Astrocytes play key roles in the regulation of brain energy metabolism, which has a major impact on brain functions, including memory, neuroprotection, resistance to oxidative stress and homeostatic tone. Energy demands of the brain are very large, as they continuously account for 20–25% of the whole body’s energy consumption. Energy supply of the brain is tightly linked to neuronal activity, providing the origin of the signals detected by the widely used functional brain imaging techniques such as functional magnetic resonance imaging and positron emission tomography. In particular, neuroenergetic coupling is regulated by astrocytes through glutamate uptake that triggers astrocytic aerobic glycolysis and leads to glucose uptake and lactate release, a mechanism known as the Astrocyte Neuron Lactate Shuttle. Other neurotransmitters such as noradrenaline and Vasoactive Intestinal Peptide mobilize glycogen, the reserve for glucose exclusively localized in astrocytes, also resulting in lactate release. Lactate is then transferred to neurons where it is used, after conversion to pyruvate, as a rapid energy substrate, and also as a signal that modulates neuronal excitability, homeostasis, and the expression of survival and plasticity genes. Importantly, glycolysis in astrocytes and more generally cerebral glucose metabolism progressively deteriorate in aging and age-associated neurodegenerative diseases such as Alzheimer’s disease. This decreased glycolysis actually represents a common feature of several neurological pathologies. Here, we review the critical role of astrocytes in the regulation of brain energy metabolism, and how dysregulation of astrocyte-mediated metabolic pathways is involved in brain hypometabolism. Further, we summarize recent efforts at preclinical and clinical stages to target brain hypometabolism for the development of new therapeutic interventions in age-related neurodegenerative diseases.

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“…The brain represents 2% of the body mass in adults, yet the energy demands to maintain adequate brain function require 20-25% of total body glucose utilisation and ~20% of the oxygen consumption [95,96]. In the adult brain, glucose is the obligate energy substrate for the production of adenosine triphosphate (ATP), except under particular circumstances where ketone bodies (e.g., during fasting) and lactate (e.g., during intense physical activity) are also utilised [97,98]. Circulating glucose enters the brain parenchyma by facilitated transport via 55-kDa glucose transporter 1 (GLUT1) on the capillary endothelial cells, and is subsequently taken up by neurons (via GLUT3) and glial cells [95,99,100].…”

Section: Neurovascular Coupling and Brain Energy Metabolismmentioning

confidence: 99%

GLP-1 Receptor Agonists in Neurodegeneration: Neurovascular Unit in the Spotlight

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Moreira

Richner

et al. 2022

Cells

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Defects in brain energy metabolism and proteopathic stress are implicated in age-related degenerative neuronopathies, exemplified by Alzheimer’s disease (AD) and Parkinson’s disease (PD). As the currently available drug regimens largely aim to mitigate cognitive decline and/or motor symptoms, there is a dire need for mechanism-based therapies that can be used to improve neuronal function and potentially slow down the underlying disease processes. In this context, a new class of pharmacological agents that achieve improved glycaemic control via the glucagon-like peptide 1 (GLP-1) receptor has attracted significant attention as putative neuroprotective agents. The experimental evidence supporting their potential therapeutic value, mainly derived from cellular and animal models of AD and PD, has been discussed in several research reports and review opinions recently. In this review article, we discuss the pathological relevance of derangements in the neurovascular unit and the significance of neuron–glia metabolic coupling in AD and PD. With this context, we also discuss some unresolved questions with regard to the potential benefits of GLP-1 agonists on the neurovascular unit (NVU), and provide examples of novel experimental paradigms that could be useful in improving our understanding regarding the neuroprotective mode of action associated with these agents.

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Fluid Brain Glycolysis: Limits, Speed, Location, Moonlighting, and the Fates of Glycogen and Lactate

Cited by 14 publications

References 77 publications

Astrocyte-neuron metabolic cooperation shapes brain activity

Astrocyte-neuron metabolic cooperation shapes brain activity

Astrocytes as Key Regulators of Brain Energy Metabolism: New Therapeutic Perspectives

GLP-1 Receptor Agonists in Neurodegeneration: Neurovascular Unit in the Spotlight

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