Brain Energy Metabolism: Focus on Astrocyte-Neuron Metabolic Cooperation

Bélanger, Marcel; Allaman, Igor; Magistretti, Pierre J.

doi:10.1016/j.cmet.2011.08.016

Cited by 1,833 publications

(1,637 citation statements)

References 130 publications

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“…Lactate and pyruvate could enter mitochondria and serve as substrates of the tricarboxylic acid cycle and oxidative phosphorylation. 29 For many years, lactate has traditionally been thought as a useless 'dead end' product of anaerobic metabolism and harmful sometimes. Its elevation in the brain signals cerebral ischemic damage.…”

Section: Discussionmentioning

confidence: 99%

Low-Level Light in Combination with Metabolic Modulators for Effective Therapy of Injured Brain

Dong

Zhang

Hamblin

et al. 2015

J Cereb Blood Flow Metab

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Vascular damage occurs frequently at the injured brain causing hypoxia and is associated with poor outcomes in the clinics. We found high levels of glycolysis, reduced adenosine triphosphate generation, and increased formation of reactive oxygen species and apoptosis in neurons under hypoxia. Strikingly, these adverse events were reversed significantly by noninvasive exposure of injured brain to low-level light (LLL). Low-level light illumination sustained the mitochondrial membrane potential, constrained cytochrome c leakage in hypoxic cells, and protected them from apoptosis, underscoring a unique property of LLL. The effect of LLL was further bolstered by combination with metabolic substrates such as pyruvate or lactate both in vivo and in vitro. The combinational treatment retained memory and learning activities of injured mice to a normal level, whereas other treatment displayed partial or severe deficiency in these cognitive functions. In accordance with well-protected learning and memory function, the hippocampal region primarily responsible for learning and memory was completely protected by combination treatment, in marked contrast to the severe loss of hippocampal tissue because of secondary damage in control mice. These data clearly suggest that energy metabolic modulators can additively or synergistically enhance the therapeutic effect of LLL in energyproducing insufficient tissue-like injured brain.

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Section: Discussionmentioning

confidence: 99%

Low-Level Light in Combination with Metabolic Modulators for Effective Therapy of Injured Brain

Dong

Zhang

Hamblin

et al. 2015

J Cereb Blood Flow Metab

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“…This shift in metabolism toward a greater emphasis on AG might well be occurring with support from astrocytes (96) that are well known for their contributions to brain AG (for a recent comprehensive review, see ref. 97).…”

Section: Discussionmentioning

confidence: 99%

Brain aerobic glycolysis and motor adaptation learning

Shannon

Vaishnavi

Vlassenko

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Ten percent to 15% of glucose used by the brain is metabolized nonoxidatively despite adequate tissue oxygenation, a process termed aerobic glycolysis (AG). Because of the known role of glycolysis in biosynthesis, we tested whether learning-induced synaptic plasticity would lead to regionally appropriate, learningdependent changes in AG. Functional MRI (fMRI) before, during, and after performance of a visual-motor adaptation task demonstrated that left Brodmann area 44 (BA44) played a key role in adaptation, with learning-related changes to activity during the task and altered resting-state, functional connectivity after the task. PET scans before and after task performance indicated a sustained increase in AG in left BA 44 accompanied by decreased oxygen consumption. Intersubject variability in behavioral adaptation rate correlated strongly with changes in AG in this region, as well as functional connectivity, which is consistent with a role for AG in synaptic plasticity.T he resting brain's energy needs are supported almost entirely by the metabolism of glucose to carbon dioxide and water (1). The first step of this process, glycolysis, requires no oxygen whereas the second step, oxidative phosphorylation, does. In the normal adult human brain, 10-15% of the glucose never reaches the second step-it is shunted away from oxidative phosphorylation despite the presence of adequate oxygen (2-5). This process is commonly referred to as aerobic glycolysis (AG).Several roles for AG have been identified, including biosynthesis (for recent reviews, see refs. 6-8), the regulation of cellular redox states (9, 10), the regulation of apoptosis (11), the provision of ATP for membrane pumps (12)(13)(14), and the regulation of cell excitability (15, 16). More recently, similar functions of AG have been observed in the posttranscriptional control of T-cell effector function (17, 18), an observation now extended to the microglia (19), where it is associated with an activated state related to inflammation as well as synaptic pruning.In the developing human brain, at a time when synaptic growth rates are highest (approximately age 10), total glucose consumption is twice that of the adult, and 30% of that glucose consumption is AG (a recent summary of this early literature is contained in ref. 20), suggesting an important role in brain development. Another remarkable feature of AG in the adult human brain is that it varies regionally (21): nearly 25% of resting glucose consumption in the medial prefrontal cortex is AG whereas AG constitutes as little as 2% glucose consumption in the cerebellum and medial temporal lobes. Correlation of these regional data with regional gene expression in the adult human brain revealed increased gene expression typical of infancy (i.e., neotony) that is related to synapse formation and growth (20).Further supporting the link between AG and plasticity are findings demonstrating that lactate, released by astrocytes and taken up by neurons, is critical for memory formation. Neuronal uptake of lactate ch...

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“…Prior studies have shown that T1ρ is sensitive to changes in pH, with signal increasing with acidity (Heo et al., 2014; Kettunen et al., 2002). Because of this, fT1ρ signal may reflect increases in acidic metabolites such as H + , glutamate, and lactate in tissue following neuronal activation (Belanger et al., 2011). We would then expect that neuronal activation would result in an increase in both BOLD and fT1ρ signal.…”

Section: Discussionmentioning

confidence: 99%

“…This technique aims to quantitatively map the spin‐lock–based T1ρ relaxation time temporally and is sensitive to chemical exchange of protons between water and amide, hydroxyl, and/or amine groups (Jin, Autio, Obata, & Kim, 2011). This chemical exchange is influenced by pH and metabolite concentration (e.g., glucose and glutamate) (Jin et al., 2011; Kettunen, Gröhn, Silvennoinen, Penttonen, & Kauppinen, 2002), which have been shown to change in response to neural activation prior to changes in blood flow (Belanger, Allaman, & Magistretti, 2011). T1ρ relaxation is also sensitive to stimulus‐induced rotary saturation (SIRS), which may directly measure neuronal currents (Witzel, Lin, Rosen, & Wald, 2008).…”

Section: Introductionmentioning

confidence: 99%

Relationship altered between functional T1ρ and BOLD signals in bipolar disorder

et al. 2017

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IntroductionFunctional neuroimaging typically relies on the blood‐oxygen‐level–dependent (BOLD) contrast, which is sensitive to the influx of oxygenated blood following neuronal activity. A new method, functional T1 relaxation in the rotating frame (fT1ρ) is thought to reflect changes in local brain metabolism, likely pH, and may more directly measure neuronal activity. These two methods were applied to study activation of the visual cortex in participants with bipolar disorder as compared to controls.MethodsThirty‐nine participants with bipolar disorder and 32 healthy controls underwent functional neuroimaging during a flashing checkerboard paradigm. Functional images were acquired in alternating blocks of BOLD and fT1ρ. Linear mixed‐effect models were used to examine the relationship between these two functional imaging modalities and to test whether that relationship was altered in bipolar disorder.Results BOLD and fT1ρ signal were strongly related in visual and cerebellar areas during the task in controls. The relationship between these two measures was reduced in bipolar disorder within the visual areas, cerebellum, striatum, and thalamus.ConclusionsThese results support a distinct mechanisms underlying BOLD and fT1ρ signals. The weakened relationship between these imaging modalities may provide a novel tool for measuring pathology in bipolar disorder and other psychiatric illnesses.

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Brain Energy Metabolism: Focus on Astrocyte-Neuron Metabolic Cooperation

Cited by 1,833 publications

References 130 publications

Low-Level Light in Combination with Metabolic Modulators for Effective Therapy of Injured Brain

Low-Level Light in Combination with Metabolic Modulators for Effective Therapy of Injured Brain

Brain aerobic glycolysis and motor adaptation learning

Relationship altered between functional T1ρ and BOLD signals in bipolar disorder

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