Aerobic glycolysis in the primate brain: reconsidering the implications for growth and maintenance

Bauernfeind, Amy L.; Barks, Sarah K.; Duka, Tetyana; Grossman, Lawrence I.; Hof, Patrick R.; Sherwood, Chet C.

doi:10.1007/s00429-013-0662-z

Cited by 91 publications

(85 citation statements)

References 227 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These patterns suggest that peak brain glucose uptake during childhood reflects neuronal plasticity in the cerebral cortex (32), which involves overproliferation of energetically costly dendritic arbors and synapses before activity-dependent pruning (33,34). Recent work shows that glucose uptake outpaces oxygen use in the human brain, and that this imbalance also peaks at the age of greatest glucose uptake in childhood, pointing to an important role of aerobic glycolysis in support of synaptic proliferation and growth (28,30). Collectively, this large increase in glucose uptake corresponds closely with the age of slowest body-weight growth.…”

Section: Discussionmentioning

confidence: 98%

“…recent work shows that the rate of glucose uptake exceeds oxygen consumption in the brain (27), with up to 30% of brain glucose not entering oxidative phosphorylation during childhood (28). This additional use of glucose, in aerobic glycolysis, contributes to protein synthesis associated with synaptic growth and other important developmental functions (28)(29)(30), yet is not reflected in measures of oxygen consumption like N 2 O, which therefore underestimate total brain glucose uptake and use.…”

Section: Significancementioning

confidence: 99%

See 1 more Smart Citation

Metabolic costs and evolutionary implications of human brain development

Kuzawa

Chugani

Grossman

et al. 2014

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

Self Cite

454

393

View full text Add to dashboard Cite

The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain's glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain-body metabolic trade-offs using the ratios of brain glucose uptake to the body's resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucose rmr% and glucose der% ). We find that glucose rmr% and glucose der% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucose rmr% and glucose der% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate.neuroimaging | diabetes | human evolution | neuronal plasticity | anthropology A prolonged period of childhood and juvenile growth is a defining feature of human life history (1-3). Compared with other great apes, human offspring are weaned early, leading to an extended period of dependence on procured resources rather than breast milk (1, 4). Although this unique human reproductive pattern is viewed as shortening the interbirth interval and thus increasing fertility (5, 6), what is less clear is why humans also grow so slowly during childhood. Although most primates grow slower than other mammals (7), human childhood and juvenile growth stand out as unusually slow even by primate and great ape standards, during which it proceeds at a pace more typical of reptiles than of mammals (8, 9). In humans, a sizeable percentage of preadult growth is deferred until the pubertal growth spurt, when growth rate markedly increases and adult size is achieved (1).Many hypotheses have been proposed to explain this slow and prolonged preadult life-stage, with most pointing to the extra time and energy required for human learning and brain development (5, 10-12). It has long been assumed that human cultural practices are sufficiently complex that they take many years to learn, which could have selected for a slowing down and extension of preadult development (13). A recent variant of this idea notes the importance of ...

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Significancementioning

confidence: 99%

Metabolic costs and evolutionary implications of human brain development

Kuzawa

Chugani

Grossman

et al. 2014

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

Self Cite

454

393

View full text Add to dashboard Cite

show abstract

“…Later, during postnatal development, aerobic glycolysis may persist to support the maturational changes of neurons, including axonal elongation, synaptogenesis and myelination. It has been speculated that aerobic glycolysis may persist in restricted regions of the brain throughout adult life for the purposes of activity-related changes at the synapse that accompany learning and memory [66]. Interestingly, the areas of the brain with the highest levels of glycolysis in adulthood are those that have the highest susceptibility to AD, suggesting they are more vulnerable to energy failure [67].…”

Section: Metabolic Reprogramming and Cellular Survivalmentioning

confidence: 99%

Preventing Alzheimer's disease by means of natural selection

Demetrius

Driver

2015

J. R. Soc. Interface.

View full text Add to dashboard Cite

The amyloid cascade model for the origin of sporadic forms of Alzheimer's disease (AD) posits that the imbalance in the production and clearance of beta-amyloid is a necessary condition for the disease. A competing theory called the entropic selection hypothesis asserts that the primary cause of sporadic AD is age-induced mitochondrial dysregulation and the following cascade of events: (i) metabolic reprogramming-the upregulation of oxidative phosphorylation in compensation for insufficient energy production in neurons, (ii) natural selection-competition between intact and reprogrammed neurons for energy substrates and (iii) propagation-the spread of the disease due to the selective advantage of neurons with upregulated metabolism. Experimental studies to evaluate the predictions of the amyloid cascade model are being continually retuned to accommodate conflicts of the predictions with empirical data. Clinical trials of treatments for AD based on anti-amyloid therapy have been unsuccessful. We contend that these anomalies and failures stem from a fundamental deficit of the amyloid hypothesis: the model derives from a nuclear-genomic perspective of sporadic AD and discounts the bioenergetic processes that characterize the progression of most age-related disorders. In this article, we review the anomalies of the amyloid model and the theoretical and empirical support for the entropic selection theory. We also discuss the new therapeutic strategies based on natural selection which the model proposes.

show abstract

“…Whether or not this brain growth deficiency is due to an energy deficit is not yet clear. However, the brain is entirely dependent on energy substrates provided by the peripheral organs [36, 37]. Thus, a strain on brain energy demands could prompt compensatory mechanisms in the periphery and the need to shunt energy to the brain may subsequently exacerbate any potential primary systemic energy deficit.…”

Section: Discussionmentioning

confidence: 99%

Abnormal Weight and Body Mass Index in Children with Juvenile Huntington’s Disease

Tereshchenko

McHugh

Lee

et al. 2015

JHD

View full text Add to dashboard Cite

Objectives To evaluate anthropometric measures of growth and development (height, weight, body mass index (BMI)) in a group of children, adolescents, and young adults diagnosed with Juvenile Onset Huntington’s Disease (JHD). Methods Growth measures for 18 JHD patients, documented prior to or shortly after diagnosis, were obtained through medical records. JHD growth measures were compared to a large sample (n=274) of healthy children, as well as the Center for Disease Control (CDC) growth norms. Results After controlling for sex and age, the JHD subjects had no significant differences in height. However, they were an average of 10% lower than controls in weight and BMI. Using CDC norms, the JHD subjects had the same pattern of normal height but decrement in weight. Length of cytosine-adenine-guanine (CAG) repeat in the huntingtin gene was significantly correlated to measures of weight with longer CAG repeats being associated with more severe weight reduction. A subset of 4 subjects had measures that pre-dated onset of any symptom and were therefore prodromal JHD (preJHD). These subjects also had a significant decrement in BMI compared to CDC norms. Conclusions Children with JHD have normal height, but significantly reduced weight and BMI, indicative of a specific deficit in body weight. As the preJHD subjects were also low in BMI, this suggests that these changes are directly due to the effect of the mutated gene on development, rather than symptom manifestation of the disease itself. Potential mechanisms of the weight decrement include energy deficiency due to mitochondrial dysfunction during development.

show abstract

Aerobic glycolysis in the primate brain: reconsidering the implications for growth and maintenance

Cited by 91 publications

References 227 publications

Metabolic costs and evolutionary implications of human brain development

Metabolic costs and evolutionary implications of human brain development

Preventing Alzheimer's disease by means of natural selection

Abnormal Weight and Body Mass Index in Children with Juvenile Huntington’s Disease

Contact Info

Product

Resources

About