Regional aerobic glycolysis in the human brain

Department of Radiology, Washington University, St. Louis, MO 63110, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 10/2010; 107(41):17757-62. DOI: 10.1073/pnas.1010459107
Source: PubMed


Aerobic glycolysis is defined as glucose utilization in excess of that used for oxidative phosphorylation despite sufficient oxygen to completely metabolize glucose to carbon dioxide and water. Aerobic glycolysis is present in the normal human brain at rest and increases locally during increased neuronal activity; yet its many biological functions have received scant attention because of a prevailing energy-centric focus on the role of glucose as substrate for oxidative phosphorylation. As an initial step in redressing this neglect, we measured the regional distribution of aerobic glycolysis with positron emission tomography in 33 neurologically normal young adults at rest. We show that the distribution of aerobic glycolysis in the brain is differentially present in previously well-described functional areas. In particular, aerobic glycolysis is significantly elevated in medial and lateral parietal and prefrontal cortices. In contrast, the cerebellum and medial temporal lobes have levels of aerobic glycolysis significantly below the brain mean. The levels of aerobic glycolysis are not strictly related to the levels of brain energy metabolism. For example, sensory cortices exhibit high metabolic rates for glucose and oxygen consumption but low rates of aerobic glycolysis. These striking regional variations in aerobic glycolysis in the normal human brain provide an opportunity to explore how brain systems differentially use the diverse cell biology of glucose in support of their functional specializations in health and disease.

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    • "It should be noted that lactate can also be formed in the presence of sufficient oxygen availability through a metabolic pathway called ''aerobic glycolysis " or ''Warburg effect " . In the brain aerobic glycolysis is a hallmark of task-induced increases in neuronal activity, (Vaishnavi et al., 2010). From the standpoint of glucose metabolism, astrocytes are predominantly glycolytic, producing lactate in the presence of oxygen while neurons are predominantly oxidative (Magistretti and Allaman, 2015). "
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    • " aerobic glycolysis under conditions of increased BACE1 activity mirrors early and predictive changes occurring in the brains of people who later develop AD . The brain areas that display this profile overlap with regions showing the greatest prevalence of Aβ pathology , future susceptibility to cell death and are predictive of cognitive decline ( Vaishnavi et al . , 2010 ; Vlassenko et al . , 2010 ) . The mechanisms underlying glucose hypometabolism in AD are not well - understood . However , mitochondrial dysfunction has been widely reported in clinical and experimental AD studies ( Lustbader et al . , 2004 ; Beal , 2005 ; Bubber et al . , 2005 ) and Aβ has been reported to accumulate in the mitochondr"
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    • "This concept has been introduced following earlier observations that simple procedures, such as handling of rats or tail pinching, increases lactate release in brain (Kuhr and Korf 1988; De Bruin et al. 1990). Numerous further studies demonstrated that lactate formation from pyruvate is a regular process which takes place also in aerobic glycolysis (Brooks 2009; Vaishnavi et al. 2010). The source of lactate in this situation – neurons or glial cells – is unclear. "
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