Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or . mil VSports app下载. Before sharing sensitive information, make sure you’re on a federal government site. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. V体育官网.

Meta-Analysis
. 2014 Jan 7;19(1):49-57.
doi: 10.1016/j.cmet.2013.11.020.

V体育ios版 - Aerobic glycolysis in the human brain is associated with development and neotenous gene expression

Manu S Goyal  1 , Michael Hawrylycz  2 , Jeremy A Miller  2 , Abraham Z Snyder  3 , Marcus E Raichle  4
Affiliations
Meta-Analysis

Aerobic glycolysis in the human brain is associated with development and neotenous gene expression

Manu S Goyal (VSports最新版本) et al. Cell Metab. .

"V体育平台登录" Abstract

Aerobic glycolysis (AG; i. e. , nonoxidative metabolism of glucose despite the presence of abundant oxygen) accounts for 10%-12% of glucose used by the adult human brain. AG varies regionally in the resting state. Brain AG may support synaptic growth and remodeling; however, data supporting this hypothesis are sparse. Here, we report on investigations on the role of AG in the human brain. Meta-analysis of prior brain glucose and oxygen metabolism studies demonstrates that AG increases during childhood, precisely when synaptic growth rates are highest. In resting adult humans, AG correlates with the persistence of gene expression typical of infancy (transcriptional neoteny). In brain regions with the highest AG, we find increased gene expression related to synapse formation and growth VSports手机版. In contrast, regions high in oxidative glucose metabolism express genes related to mitochondria and synaptic transmission. Our results suggest that brain AG supports developmental processes, particularly those required for synapse formation and growth. .

PubMed Disclaimer

Figures

Figure 1
Figure 1. Human brain AG varies regionally in healthy adults
AG was measured as previously described (Vaishnavi et al. 2010) in 33 normal young adults. AG, expressed as the glycolytic index, is illustrated here on the lateral and medial brain surface. Computed AG has been geodesically (parallel to the cortical surface) smoothed. The highest levels of AG occur in the medial frontal gyrus, precuneus, and posterior cingulate cortex, as previously reported.
Figure 2
Figure 2. see also Table S1. Brain metabolism across the lifespan
As discussed in the main text, data were gathered from 15 different studies dating back to 1953. (A) Whole brain or cerebral total glucose consumption rates (blue circles) and a fit obtained using loessR (blue line, see Experimental Procedures for details) demonstrate an approximate doubling of CMRglc during early childhood. The expected glucose consumption based on measured oxygen consumption rates is also plotted (red circles and line). This also increases during early childhood, though less than the measured changes in CMRglc, suggesting that approximately 30% of the CMRglc during childhood is in excess of oxygen consumption (i.e., aerobic glycolysis). (B) CMRglc (blue), CMRO2 (red), and CBF (orange) were plotted across the lifespan as normalized proportions of average adult values. This analysis again shows an approximate 2-fold rise in CMRglc and 1.5-fold rise in CMRO2 during early childhood. Interestingly, CBF also increases 2-fold during early childhood, matching the changes in CMRglc, but then appears to more closely follow changes in CMRO2 during adulthood. The raw and normalized data are shown in Table S1.
Figure 3
Figure 3. Transcriptional neoteny regionally correlates with aerobic glycolysis
We assessed the transcriptional neoteny in each of 15 regions from the BSS as compared to the cerebellum. A gene was defined as neotenous in a particular region if its expression demonstrated delayed, prolonged, or potentiated expression as compared to its expression in the cerebellum. Thus, by definition, there are zero neotenous genes in the cerebellum (CBC) as compared to itself. The number of neotenous genes in each region, that is, the regional neoteny index, increases in relation to aerobic glycolysis (r = 0.77, Pearson correlation, p=0.0008, 95% CI 0.43–0.92). The median age-shift across all genes for each region as compared to the cerebellum also correlates with aerobic glycolysis (r = 0.71, Pearson correlation, p=0.003, 95% CI 0.31–0.90). Regions are named according to the BSS (Kang et al., 2011): CBC = cerebellum, MD = thalamus, AMY = amygdala, HIP = hippocampus, ITC = inferior temporal cortex, STR = striatum, V1C = primary visual cortex, STC = superior temporal cortex, A1C = auditory cortex, IPC = inferior parietal cortex, M1C = primary motor cortex, S1C = primary somatosensory cortex, MFC = medial frontal cortex, OFC = orbital frontal cortex, DFC = dorsal frontal cortex, VFC = ventral frontal cortex.
Figure 4
Figure 4. Expression of the 116 glycolytic genes consistently expressed in glycolytic regions of the adult human brain progressively rises and persists in the cortex, particularly neocortical areas
(A) The expression of the 116 genes most consistently correlating with aerobic glycolysis in adults is plotted across the lifespan in the BrainSpan Study. Lines are smoothed and normalized group averages. Shaded regions represent 95% confidence intervals of the mean. The first few months of post-conception fetal life are associated with parallel increases in expression across the brain. However, a dramatic divergence occurs at mid-gestation, with expression failing in the cerebellum (red line), stabilizing in the diencephalon (orange), and continuing to increase in the striatum (green) and, even more so, in the cerebral cortex (blue). (B) Within the postnatal cerebral cortex, the 116 genes are most highly expressed in neocortex, particularly in association areas (dark blue line), slightly (but not significantly) less so in primary sensorimotor regions (teal line), and significantly less so in the hippocampus and amygdala (skyblue). The overall relationship among these regions suggests that these genes are more likely to persist at higher levels during adulthood in regions associated with high aerobic glycolysis.
Figure 5
Figure 5. see also Figure S2 and Tables S5-S6. Aerobic glycolysis is associated with a distinct spatio-temporal transcriptional profile compared to CMRglc
(A) Genes in the AHBA were clustered using WGCNA (see text). Node connections represent inter-nodal eigengene correlations. Spatial grouping in the figure represents gene co-expression. Correlations between each eigengene and total glucose consumption (CMRglc) or aerobic glycolysis were assessed. Node size and color (green = low, red = high) represent eigengene correlation with either CMRglc (top) or aerobic glycolysis (bottom). Aerobic glycolysis is associated with gene clusters surrounding A19. In contrast, CMRglc is associated gene clusters near A4. (B) Mean correlations between CMRglc vs. AG and eigengenes representing gene clusters surrounding A4 and A19. According to DAVID gene ontology analysis (Table S5), A4 and adjacent (A3, A6, A13, A26, and A29) gene clusters are associated with mitochondria, Golgi apparatus, synaptic transmission, and protein transport. In contrast, gene clusters surrounding A19 (A14, A21, A30, A31, and A32) are associated with synapses and dendrites, neuron projection development, calcium binding, response to glucose, and “learning.” Error bars represent standard error (S.E.M.) in the correlations for the five clusters in each group.
See this image and copyright information in PMC

"VSports最新版本" Comment in

V体育平台登录 - References

    1. ABHA Allen Brain Human Atlas [Internet] Seattle (WA): Allen Institute for Brain Science; ©2009. Available from: http://www.brain-map.org.
    1. Altman DI, Perlman JM, Volpe JJ, Powers WJ. Cerebral oxygen metabolism in newborns. Pediatrics. 1993;92:99–104. - PubMed
    1. Attwell D, Laughlin SB. An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab. 2001;21:1133–1145. - PubMed
    1. Barros LF. Metabolic signaling by lactate in the brain. Trends in neurosciences. 2013;36:396–404. - PubMed (V体育安卓版)
    1. Boyle PJ, Scott JC, Krentz AJ, Nagy RJ, Comstock E, Hoffman C. Diminished brain glucose metabolism is a significant determinant for falling rates of systemic glucose utilization during sleep in normal humans. The Journal of clinical investigation. 1994;93:529–535. - PMC - PubMed

Substances (V体育安卓版)