Brain Structure and Function

, Volume 219, Issue 4, pp 1149–1167

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

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


Glucose metabolism produces, by oxidative phosphorylation, more than 15 times the amount of energy generated by aerobic glycolysis. Nonetheless, aerobic glycolysis remains a prevalent metabolic pathway in the brain. Here we review evidence suggesting that this pathway contributes essential molecules to the biomass of the brain. Aerobic metabolism is the dominant metabolic pathway during early postnatal development when lipids and proteins are needed for the processes of axonal elongation, synaptogenesis, and myelination. Furthermore, aerobic metabolism may continue into adulthood to supply biomolecules for activity-related changes at the synapse and turnover of constituent structural components of neurons. Conversely, oxidative phosphorylation appears to be the main metabolic support for synaptic transmission, and, therefore, this pathway seems to be more dominant in brain structures and at time points in the lifespan that are characterized by increased synaptic density. We present the case for differing relationships between aerobic glycolysis and oxidative phosphorylation across primates in association with species-specific variation in neurodevelopmental trajectories. In doing so, we provide an alternative interpretation for the assessment of radiolabeled glucose positron emission tomography studies that regularly attribute increases in glucose uptake to neural activity alone, and propose a new model for the contribution of metabolic pathways for energetic demand and neural tissue growth. We conclude that comparative studies of metabolic appropriation in the brain may contribute to the discussion of human cognitive evolution and to the understanding of human-specific aging and the etiology of neuropsychiatric diseases.


Aerobic gycolysis Oxidative phosphorylation Brain energetics Default mode network Evolution 



Acetyl coenzyme A


Alzheimer’s disease






Default mode network


Dorsomedial prefrontal cortex


Lactate dehydrogenase


Nicotinamide adenine dinucleotide (NAD+), reduced state


Neurofibrillary tangle


Posterior cingulate cortex


Positron emission tomography


Pittsburgh compound B


Pentose phosphate pathway


Reactive oxygen species


Ventromedial prefrontal cortex


  1. Aiello LC, Wheeler P (1995) The expensive-tissue hypothesis: the brain and the digestive system in human and primate evolution. Curr Anthropol 36:199–221Google Scholar
  2. Akram A, Christoffel D, Rocher AB, Bouras C, Kovari E, Perl DP, Morrison JH, Herrmann FR, Haroutunian V, Giannakopoulos P, Hof PR (2008) Stereologic estimates of total spinophilin-immunoreactive spine number in area 9 and the CA1 field: relationship with the progression of Alzheimer’s disease. Neurobiol Aging 29:1296–1307PubMedCentralPubMedGoogle Scholar
  3. Altman DI, Perlman JM, Volpe JJ, Powers WJ (1993) Cerebral oxygen metabolism in newborns. Pediatrics 92:99–104PubMedGoogle Scholar
  4. Amato S, Liu X, Zheng B, Cantley L, Rakic P, Man H-Y (2011) AMP-activated protein kinase regulates neuronal polarization by interfering with PI 3-kinase localization. Science 332:247–251PubMedCentralPubMedGoogle Scholar
  5. Ames A (1992) Energy requirements of CNS cells as related to their function and to their vulnerability to ischemia: a commentary based on studies on retina. Can J Physiol Pharmacol 34:S158–S164Google Scholar
  6. Ames A (2000) CNS energy metabolism as related to function. Brain Res Rev 34:42–68PubMedGoogle Scholar
  7. Anderson B, Rutledge V (1996) Age and hemisphere effects on dendritic structure. Brain 119:1983–1990PubMedGoogle Scholar
  8. Andrews-Hanna JR, Snyder AZ, Vincent JL, Lustig C, Head D, Raichle ME, Buckner RL (2007) Disruption of large-scale brain systems in advanced aging. Neuron 56:924–935PubMedCentralPubMedGoogle Scholar
  9. Anglin RES, Mazurek MF, Tarnopolsky MA, Rosebush PI (2012) The mitochondrial genome and psychiatric illness. Am J Med Genet 159B:749–759PubMedGoogle Scholar
  10. Antonicka H, Leary SC, Guercin G-H, Agar JN, Horvath R, Kennaway NG, Harding CO, Jaksch M, Shoubridge EA (2003) Mutations in COX10 result in a defect in mitochondrial heme A biosynthesis and account for multiple, early-onset clinical phenotypes associated with isolated COX deficiency. Hum Mol Genet 12:2693–2702PubMedGoogle Scholar
  11. Atkin TA, MacAskill AF, Brandon NJ, Kittler JT (2011) Disrupted in schizophrenia-1 regulates intracellular trafficking of mitochondria in neurons. Mol Psychiatry 16:122–124PubMedGoogle Scholar
  12. Attwell D, Laughlin SB (2001) An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab 21:1133–1145PubMedGoogle Scholar
  13. Barks SK, Parr LA, Rilling JK (2013) The default mode network in chimpanzees (Pan troglodytes) is similar to that of humans. Cereb Cortex. doi:10.1093/cercor/bht253 PubMedGoogle Scholar
  14. Barrickman NL, Bastian ML, Isler K, van Schaik CP (2008) Life history costs and benefits of encephalization: a comparative test using data from long-term studies of primates in the wild. J Hum Evol 54:568–590PubMedGoogle Scholar
  15. Barton RA, Capellini I (2011) Maternal investment, life histories, and the costs of brain growth in mammals. Proc Natl Acad Sci USA 108:6169–6174PubMedCentralPubMedGoogle Scholar
  16. Baumann N, Pham-Dinh D (2001) Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev 81:871–925PubMedGoogle Scholar
  17. Beckman KB, Ames BN (1998) The free radical theory of aging matures. Physiol Rev 78:547–581PubMedGoogle Scholar
  18. Bianchi S, Stimpson CD, Duka T, Larsen M, Janssen WGM, Collins Z, Bauernfeind AL, Schapiro SJ, Baze WB, McArthur MJ, Hopkins WD, Wildman DE, Lipovich L, Kuzawa CW, Jacobs B, Hof PR, Sherwood CC (2013) Synaptogenesis and development of pyramidal neuron dendritic morphology in the chimpanzee neocortex resembles humans. Proc Natl Acad Sci USA 110:10395–10401PubMedCentralPubMedGoogle Scholar
  19. Bigl M, Bleyl AD, Zedlick D, Arendt T, Bigl V, Eschrich K (1996) Changes of activity and isozyme pattern of phosphofructokinase in the brains of patients with Alzheimer’s disease. J Neurochem 67:1164–1171PubMedGoogle Scholar
  20. Bigl M, Brückner MK, Arendt T, Bigl V, Eschrich K (1999) Activities of key glycolytic enzymes in the brains of patients with Alzheimer’s disease. J Neural Transm 106:499–511PubMedGoogle Scholar
  21. Bogin B (1997) Evolutionary hypotheses for human childhood. Yearb Phys Anthropol 40:63–89Google Scholar
  22. Bourgeois JP, Goldman-Rakic PS, Rakic P (1994) Synaptogenesis in the prefrontal cortex of rhesus monkeys. Cereb Cortex 4:78–96PubMedGoogle Scholar
  23. Bowley MP, Cabral H, Rosene DL, Peters A (2010) Age changes in myelinated nerve fibers of the cingulate bundle and corpus callosum in the rhesus monkey. J Comp Neurol 518:3046–3064PubMedCentralPubMedGoogle Scholar
  24. Boyle PJ, Scott JC, Krentz AJ, Nagy RJ, Comstock E, Hoffman C (1994) Diminished brain glucose metabolism is a significant determinant for falling rates of systemic glucose utilization during sleep in normal humans. J Clin Invest 93:529–535PubMedCentralPubMedGoogle Scholar
  25. Brand KA, Hermfisse U (1997) Aerobic glycolysis by proliferating cells: a protective strategy against reactive oxygen species. FASEB J 11:388–395PubMedGoogle Scholar
  26. Brooks GA (2009) Cell-cell and intracellular lactate shuttles. J Physiol 587:5591–5600PubMedCentralPubMedGoogle Scholar
  27. Brown AM, Wender R, Ransom BR (2001) Metabolic substrates other than glucose support axon function in central white matter. J Neurosci Res 66:839–843PubMedGoogle Scholar
  28. Buckner RL (2011) The serendipitous discovery of the brain’s default network. Neuroimage 62:1137–1145PubMedGoogle Scholar
  29. Buckner RL, Carroll DC (2007) Self-projection and the brain. Trends Cogn Sci 11:49–57PubMedGoogle Scholar
  30. Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 1124:1–38PubMedGoogle Scholar
  31. Bufill E, Agustí J, Blesa R (2011) Human neoteny revisited: the case of synaptic plasticity. Am J Hum Biol 23:729–739PubMedGoogle Scholar
  32. Bussière T, Giannakopoulos P, Bouras C, Perl DP, Morrison JH, Hof PR (2003a) Progressive degeneration of nonphosphorylated neurofilament protein-enriched pyramidal neurons predicts cognitive impairment in Alzheimer’s disease: stereologic analysis of prefrontal cortex area 9. J Comp Neurol 463:281–302PubMedGoogle Scholar
  33. Bussière T, Gold G, Kövari E, Giannakopoulos P, Bouras C, Perl DP, Morrison JH, Hof PR (2003b) Stereologic analysis of neurofibrillary tangle formation in prefrontal cortex area 9 in aging and Alzheimer’s disease. Neuroscience 117:577–592PubMedGoogle Scholar
  34. Cáceres M, Lachuer J, Zapala MA, Kudo L, Geschwind DH, Lockhart DJ, Preuss TM, Barlow C (2003) Elevated gene expression levels distinguish human from non-human primate brains. Proc Natl Acad Sci USA 100:13030–13035PubMedCentralPubMedGoogle Scholar
  35. Cavanna AE, Trimble MR (2006) The precuneus: a review of its functional anatomy and behavioural correlates. Brain 129:564–583PubMedGoogle Scholar
  36. Chandrasekaran K, Giordano T, Brady DR, Stoll J, Martin LJ, Rapoport SI (1994) Impairment in mitochondrial cytochrome oxidase gene expression in Alzheimer disease. Mol Brain Res 24:336–340PubMedGoogle Scholar
  37. Chugani HT (1998) A critical period of brain development: studies of cerebral glucose utilization with PET. Prev Med 27:184–188PubMedGoogle Scholar
  38. Chugani HT, Phelps ME, Mazziotta JC (1987) Positron emission tomography study of human brain functional development. Ann Neurol 22:487–497PubMedGoogle Scholar
  39. Clarke DD, Sokoloff L (1999) Circulation and energy metabolism of the brain. In: Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD (eds) Basic neurochemistry, 6th edn. Lippincott-Raven, Philadelphia, pp 637–670Google Scholar
  40. Constantinidis C, Steinmetz MA (2001) Neuronal responses in area 7a to multiple-stimulus displays: I. Neurons encode the location of the salient stimulus. Cereb Cortex 11:581–591PubMedGoogle Scholar
  41. Coskun PE, Beal MF, Wallace DC (2004) Alzheimer’s brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication. Proc Natl Acad Sci USA 101:10726–10731PubMedCentralPubMedGoogle Scholar
  42. Coskun PE, Wyrembak J, Derbereva O, Melkonian G, Doran E, Lott IT, Head E, Cotman CW, Wallace DC (2010) Systemic mitochondrial dysfunction and the etiology of Alzheimer’s disease and Down syndrome dementia. J Alzheimers Dis 20:S293–S310PubMedGoogle Scholar
  43. Coskun P, Wyrembak J, Schriner SE, Chen H, Marciniack C, LaFerla F, Wallace DC (2012) A mitochondrial etiology of Alzheimer and Parkinson disease. Biochim Biophys Acta 1820:553–564PubMedCentralPubMedGoogle Scholar
  44. De Bock K, Georgiadou M, Schoors S, Kuchnio A, Wong BW, Cantelmo AR, Quaegebeur A, Ghesquière B, Cauwenberghs S, Eelen G, Phng L-K, Betz I, Tembuyser B, Brepoels K, Welti J, Geudens I, Segura I, Cruys B, Bifari F, Decimo I, Blanco R, Wyns S, Vangindertael J, Rocha S, Collins RT, Munck S, Daelemans D, Imamura H, Devlieger R, Rider M, Van Veldhoven PP, Schuit F, Bartrons R, Hofkens J, Fraisl P, Telang S, DeBerardinis RJ, Schoonjans L, Vinckier S, Chesney J, Gerhardt H, Dewerchin M, Carmeliet P (2013) Role of PFKFB3-driven glycolysis in vessel sprouting. Cell 154:651–663PubMedGoogle Scholar
  45. Diano S, Liu Z-W, Jeong JK, Dietrich MO, Ruan H-B, Kim E, Suyama S, Kelly K, Gyengesi E, Arbiser JL, Belsham DD, Sarruf DA, Schwartz MW, Bennett AM, Shanabrough M, Mobbs CV, Yang X, Gao X-B, Horvath TL (2011) Peroxisome proliferation-associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity. Nat Med 17:1121–1127PubMedCentralPubMedGoogle Scholar
  46. Diaz F (2005) Mice lacking COX10 in skeletal muscle recapitulate the phenotype of progressive mitochondrial myopathies associated with cytochrome c oxidase deficiency. Hum Mol Genet 14:2737–2748PubMedCentralPubMedGoogle Scholar
  47. Dienel GA, Hertz L (2001) Glucose and lactate metabolism during brain activation. J Neurosci Res 66:824–838PubMedGoogle Scholar
  48. DiMauro S, Schon EA (2008) Mitochondrial disorders in the nervous system. Annu Rev Neurosci 31:91–123PubMedGoogle Scholar
  49. Dobbing J, Sands J (1979) Comparative aspects of the brain growth spurt. Early Hum Dev 311:79–83Google Scholar
  50. Duan H, Wearne SL, Rocher AB, Macedo A, Morrison JH, Hof PR (2003) Age-related dendritic and spine changes in corticocortically projecting neurons in macaque monkeys. Cereb Cortex 13:950–961PubMedGoogle Scholar
  51. Dumitriu D, Hao J, Hara Y, Kaufmann J, Janssen WGM, Lou W, Rapp PR, Morrison JH (2010) Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment. J Neurosci 30:7507–7515PubMedCentralPubMedGoogle Scholar
  52. Ehlers MD (2003) Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system. Nat Neurosci 6:231–242PubMedGoogle Scholar
  53. Elston GN, Benavides-Piccione R, DeFelipe J (2001) The pyramidal cell in cognition: a comparative study in human and monkey. J Neurosci 21:RC163PubMedGoogle Scholar
  54. Erecinska M, Cherian S, Silver IA (2004) Energy metabolism in mammalian brain during development. Prog Neurobiol 73:397–445PubMedGoogle Scholar
  55. Eykelenboom JE, Briggs GJ, Bradshaw NJ, Soares DC, Ogawa F, Christie S, Malavasi ELV, Makedonopoulou P, Mackie S, Malloy MP, Wear MA, Blackburn EA, Bramham J, McIntosh AM, Blackwood DH, Muir WJ, Porteous DJ, Millar JK (2012) A t(1;11) translocation linked to schizophrenia and affective disorders gives rise to aberrant chimeric DISC1 transcripts that encode structurally altered, deleterious mitochondrial proteins. Hum Mol Genet 21:3374–3386PubMedCentralPubMedGoogle Scholar
  56. Foley RA, Lee PC (1991) Ecology and energetics of encephalization in hominid evolution. Phil Trans R Soc B 334:223–232PubMedGoogle Scholar
  57. Fox P, Raichle M, Mintun M, Dence C (1988) Nonoxidative glucose consumption during focal physiologic neural activity. Science 241:462–464PubMedGoogle Scholar
  58. Fraser HB, Khaitovich P, Plotkin JB, Pääbo S, Eisen MB (2005) Aging and gene expression in the primate brain. PLoS Biol 3:e274PubMedCentralPubMedGoogle Scholar
  59. Fu X, Giavalisco P, Liu X, Catchpole G, Fu N, Ning Z-B, Guo S, Yan Z, Somel M, Pääbo S, Zeng R, Willmitzer L, Khaitovich P (2011) Rapid metabolic evolution in human prefrontal cortex. Proc Natl Acad Sci USA 108:6181–6186PubMedCentralPubMedGoogle Scholar
  60. Fukuyama R, Hatanpää K, Rapoport SI, Chandrasekaran K (1996) Gene expression of ND4, a subunit of complex I of oxidative phosphorylation in mitochondria, is decreased in temporal cortex of brains of Alzheimer’s disease patients. Brain Res 713:290–293PubMedGoogle Scholar
  61. Fünfschilling U, Supplie LM, Mahad D, Boretius S, Saab AS, Edgar J, Brinkmann BG, Kassmann CM, Tzvetanova ID, Möbius W, Diaz F, Meijer D, Suter U, Hamprecht B, Sereda MW, Moraes CT, Frahm J, Goebbels S, Nave KA (2012) Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature 485:517–521PubMedCentralPubMedGoogle Scholar
  62. Gatenby RA, Gillies RJ (2004) Why do cancers have high aerobic glycolysis? Nat Rev Cancer 4:891–899PubMedGoogle Scholar
  63. Gearing M, Rebeck GW, Hyman BT, Tigges J, Mirra SS (1994) Neuropathology and apolipoprotein E profile of aged chimpanzees: implications for Alzheimer disease. Proc Natl Acad Sci USA 91:9382–9386PubMedCentralPubMedGoogle Scholar
  64. Gearing M, Tigges J, Mori H, Mirra SS (1996) Aβ40 is a major form of β-amyloid in nonhuman primates. Neurobiol Aging 17:903–908PubMedGoogle Scholar
  65. Gearing M, Tigges J, Mori H, Mirra SS (1997) β-amyloid (Aβ) deposition in the brains of aged orangutans. Neurobiol Aging 18:139–146PubMedGoogle Scholar
  66. Geula C, Wu CK, Saroff D, Lorenzo A, Yuan M, Yankner BA (1998) Aging renders the brain vulnerable to amyloid beta-protein neurotoxicity. Nat Med 4:827–831PubMedGoogle Scholar
  67. Giannakopoulos P, Herrmann FR, Bussière T, Bouras C, Kövari E, Perl DP, Morrison JH, Hof PR (2003) Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease. Neurology 60:1495–1500PubMedGoogle Scholar
  68. Gibson KR (1970) Sequence of myelinization in the brain of Macaca mulatta. Dissertation, University of California, BerkeleyGoogle Scholar
  69. Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, Paus T, Evans AC, Rapoport JL (1999) Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci 2:861–863PubMedGoogle Scholar
  70. Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, Nugent TF, Herman DH, Clasen LS, Toga AW, Rapoport JL, Thompson PM (2004) Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci USA 101:8174–8179PubMedCentralPubMedGoogle Scholar
  71. Goldberg JL (2003) How does an axon grow? Genes Dev 17:941–958PubMedGoogle Scholar
  72. Goldberg A, Wildman DE, Schmidt TR, Huttemann M, Goodman M, Weiss ML, Grossman LI (2003) Adaptive evolution of cytochrome c oxidase subunit VIII in anthropoid primates. Proc Natl Acad Sci USA 100:5873–5878PubMedCentralPubMedGoogle Scholar
  73. Goldman-Rakic PS (1987) Development of cortical circuitry and cognitive function. Child Dev 58:601–622PubMedGoogle Scholar
  74. Goodman M, Syner FN, Stimson CW, Rankin JJ (1969) Phylogenetic changes in the proportions of two kinds of lactate dehydrogenase in primate brain regions. Brain Res 14:447–459PubMedGoogle Scholar
  75. Gordon GRJ, Choi HB, Rungta RL, Ellis-Davies GCR, MacVicar BA (2008) Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature 456:745–749PubMedGoogle Scholar
  76. Gould E (2007) How widespread is adult neurogenesis in mammals? Nat Rev Neurosci 8:481–488PubMedGoogle Scholar
  77. Gregson NA, Williams PL (1969) A comparative study of brain and liver mitochondria from new-born and adult rats. J Neurochem 16:617–626PubMedGoogle Scholar
  78. Greicius MD, Srivastava G, Reiss AL, Menon V (2004) Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci USA 101:4637–4642PubMedCentralPubMedGoogle Scholar
  79. Grèzes J, Fonlupt P, Bertenthal B, Delon-Martin C, Segebarth C, Decety J (2001) Does perception of biological motion rely on specific brain regions? Neuroimage 13:775–785PubMedGoogle Scholar
  80. Grossman ED, Blake R (2001) Brain activity evoked by inverted and imagined biological motion. Vision Res 41:1475–1482PubMedGoogle Scholar
  81. Grossman LI, Schmidt TR, Wildman DE, Goodman M (2001) Molecular evolution of aerobic energy metabolism in primates. Mol Phylogenet Evol 18:26–36PubMedGoogle Scholar
  82. Grossman LI, Wildman DE, Schmidt TR, Goodman M (2004) Accelerated evolution of the electron transport chain in anthropoid primates. Trends Genet 20:578–585PubMedGoogle Scholar
  83. Gusnard DA, Raichle ME (2001) Searching for a baseline: functional imaging and the resting human brain. Nat Rev Neurosci 2:685–694PubMedGoogle Scholar
  84. Gusnard DA, Akbudak E, Shulman GL, Raichle ME (2001) Medial prefrontal cortex and self-referential mental activity: relation to a default mode of brain function. Proc Natl Acad Sci USA 98:4259–4264PubMedCentralPubMedGoogle Scholar
  85. Hall CN, Klein-Flügge MC, Howarth C, Attwell D (2012) Oxidative phosphorylation, not glycolysis, powers presynaptic and postsynaptic mechanisms underlying brain information processing. J Neurosci 32:8940–8951PubMedCentralPubMedGoogle Scholar
  86. Haroutunian V, Davies P, Vianna C, Buxbaum JD, Purohit DP (2007) Tau protein abnormalities associated with the progression of Alzheimer disease type dementia. Neurobiol Aging 28:1–7PubMedGoogle Scholar
  87. Harris JJ, Jolivet R, Attwell D (2012) Synaptic energy use and supply. Neuron 75:762–777PubMedGoogle Scholar
  88. Hayden BY, Smith DV, Platt ML (2009) Electrophysiological correlates of default-mode processing in macaque posterior cingulate cortex. Proc Natl Acad Sci USA 106:5948–5953PubMedCentralPubMedGoogle Scholar
  89. Hensch TK (2004) Critical period regulation. Annu Rev Neurosci 27:549–579PubMedGoogle Scholar
  90. Hertz L (2004) The astrocyte-neuron lactate shuttle: a challenge of a challenge. J Cereb Blood Flow Metab 24:1241–1248PubMedGoogle Scholar
  91. Hevner RF, Wong-Riley MT (1991) Neuronal expression of nuclear and mitochondrial genes for cytochrome oxidase (CO) subunits analyzed by in situ hybridization: comparison with CO activity and protein. J Neurosci 11:1942–1958PubMedGoogle Scholar
  92. Hill J, Inder T, Neil J, Dierker D, Harwell J, Van Essen D (2010) Similar patterns of cortical expansion during human development and evolution. Proc Natl Acad Sci USA 107:13135–13140PubMedCentralPubMedGoogle Scholar
  93. Hof PR, Morrison JH (2004) The aging brain: morphomolecular senescence of cortical circuits. Trends Neurosci 27:607–613PubMedGoogle Scholar
  94. Hof PR, Cox K, Morrison JH (1990) Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer’s disease: I. Superior frontal and inferior temporal cortex. J Comp Neurol 301:44–54PubMedGoogle Scholar
  95. Hof PR, Gilissen EP, Sherwood CC, Duan H, Lee PWH, Delman BN, Naidich TP, Gannon PJ, Perl DP, Erwin JM (2002) Comparative neuropathology of brain aging in primates. In: Erwin JM, Hof PR (eds) Aging in nonhuman primates. Interdiscipl Top Gerontol, vol 31. Karger, Basel, pp 130–154Google Scholar
  96. Hof PR, Bussière T, Gold G, Kövari E, Giannakopoulos P, Bouras C, Perl DP, Morrison JH (2003) Stereologic evidence for persistence of viable neurons in layer II of the entorhinal cortex and the CA1 field in Alzheimer disease. J Neuropathol Exp Neurol 62:55–67PubMedGoogle Scholar
  97. Hofman MA (1983) Energy metabolism, brain size and longevity in mammals. Quarterly Rev Biol 58:495–512Google Scholar
  98. Horman S, Browne GJ, Krause U, Patel JV, Vertommen D, Bertrand L, Lavoinne A, Hue L, Proud CG, Rider MH (2002) Activation of AMP-activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis. Curr Biol 12:1419–1423PubMedGoogle Scholar
  99. Hovda DA, Chugani HT, Villablanca JR, Badie B, Sutton RL (1992) Maturation of cerebral oxidative metabolism in the cat: a cytochrome oxidase histochemistry study. J Cereb Blood Flow Metab 12:1039–1048PubMedGoogle Scholar
  100. Hovda DA, Villablanca JR, Chugani HT, Barrio JR (2006) Metabolic maturation of the brain: a study of local cerebral protein synthesis in the developing cat. Brain Res 1113:54–63PubMedGoogle Scholar
  101. Hüttemann M, Helling S, Sanderson TH, Sinkler C, Samavati L, Mahapatra G, Varughese A, Lu G, Liu J, Ramzan R, Vogt S, Grossman LI, Doan JW, Marcus K, Lee I (2011) Regulation of mitochondrial respiration and apoptosis through cell signaling: cytochrome c oxidase and cytochrome c in ischemia/reperfusion injury and inflammation. Biochim Biophys Acta 1817:598–609PubMedCentralPubMedGoogle Scholar
  102. Huttenlocher PR (1990) Morphometric study of human cerebral cortex development. Neuropsychologia 28:517–527PubMedGoogle Scholar
  103. Huttenlocher PR, Dabholkar AS (1997) Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol 387:167–178PubMedGoogle Scholar
  104. Jacobs B, Chugani HT, Allada V, Chen S, Phelps ME, Pollack DB, Raleigh MJ (1995) Developmental changes in brain metabolism in sedated rhesus macaques and vervet monkeys revealed by positron emission tomography. Cereb Cortex 5:222–233PubMedGoogle Scholar
  105. Jacobs B, Driscoll L, Schall M (1997) Life-span dendritic and spine changes in areas 10 and 18 of human cortex: a quantitative Golgi study. J Comp Neurol 386:661–680PubMedGoogle Scholar
  106. Jacobs B, Schall M, Prather M, Kapler E, Driscoll L, Baca S, Jacobs J, Ford K, Wainwright M, Treml M (2001) Regional dendritic and spine variation in human cerebral cortex: a quantitative Golgi study. Cereb Cortex 11:558–571PubMedGoogle Scholar
  107. Jareb M, Banker G (1997) Inhibition of axonal growth by brefeldin A in hippocampal neurons in culture. J Neurosci 17:8955–8963PubMedGoogle Scholar
  108. Jenkins IH, Brooks DJ, Nixon PD, Frackowiak RS, Passingham RE (1994) Motor sequence learning: a study with positron emission tomography. J Neurosci 14:3775–3790PubMedGoogle Scholar
  109. Kabaso D, Coskren PJ, Henry BI, Hof PR, Wearne SL (2009) The electrotonic structure of pyramidal neurons contributing to prefrontal cortical circuits in macaque monkeys is significantly altered in aging. Cereb Cortex 19:2248–2268PubMedCentralPubMedGoogle Scholar
  110. Karbowski J (2011) Scaling of brain metabolism and blood flow in relation to capillary and neural scaling. PLoS One 6:e26709PubMedCentralPubMedGoogle Scholar
  111. Kasischke KA, Vishwasrao HD, Fisher PJ, Zipfel WR, Webb WW (2004) Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science 305:99–103PubMedGoogle Scholar
  112. Kaufmann P, Sano MC, Jhung S, Engelstadt K, De Vivo DC (2002) Psychiatric symptoms are common features of clinical syndromes associated with mitochondrial DNA point mutations. Neurology 58:A315 (abstract)Google Scholar
  113. Kaufmann P, Shungu DC, Sano MC, Jhung S, Engelstad K, Mitsis E, Mao X, Shanske S, Hirano M, DiMauro S, De Vivo DC (2004) Cerebral lactic acidosis correlates with neurological impairment in MELAS. Neurology 62:1297–1302PubMedGoogle Scholar
  114. Kennedy C, Sakurada O, Shinohara M, Jehle J, Sokoloff L (1978) Local cerebral glucose utilization in the normal conscious macaque monkey. Ann Neurol 4:293–301PubMedGoogle Scholar
  115. Kimura N, Nakamura S, Goto N, Narushima E, Hara I, Shichiri S, Saitou K, Nose M, Hayashi T, Kawamura S, Yoshikawa Y (2001) Senile plaques in an aged western lowland gorilla. Exp Anim 50:77–81PubMedGoogle Scholar
  116. Kimura N, Tanemura K, Nakamura S, Takashima A, Ono F, Sakakibara I, Ishii Y, Kyuwa S, Yoshikawa Y (2003) Age-related changes of Alzheimer’s disease-associated proteins in cynomolgus monkey brains. Biochem Biophys Res Commun 310:303–311 Google Scholar
  117. Kirkwood TB, Austad SN (2000) Why do we age? Nature 408:233–238PubMedGoogle Scholar
  118. Kleiber M (1932) Body size and metabolism. Hilgardia 6:315–353Google Scholar
  119. Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, Bergström M, Savitcheva I, Huang G, Estrada S, Ausén B, Debnath ML, Barletta J, Price JC, Sandell J, Lopresti BJ, Wall A, Koivisto P, Antoni G, Mathis CA, Långström B (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh compound-B. Ann Neurol 55:306–319PubMedGoogle Scholar
  120. Knott GW, Holtmaat A, Wilbrecht L, Welker E, Svoboda K (2006) Spine growth precedes synapse formation in the adult neocortex in vivo. Nat Neurosci 9:1117–1124PubMedGoogle Scholar
  121. Kojima T, Onoe H, Hikosaka K, Tsutsui K-I, Tsukada H, Watanabe M (2009) Default mode of brain activity demonstrated by positron emission tomography imaging in awake monkeys: higher rest-related than working memory-related activity in medial cortical areas. J Neurosci 29:14463–14471PubMedGoogle Scholar
  122. Kornack DR, Rakic P (1999) Continuation of neurogenesis in the hippocampus of the adult macaque monkey. Proc Natl Acad Sci USA 96:5768–5773PubMedCentralPubMedGoogle Scholar
  123. Kornack DR, Rakic P (2001) The generation, migration, and differentiation of olfactory neurons in the adult primate brain. Proc Natl Acad Sci USA 98:4752–4757PubMedCentralPubMedGoogle Scholar
  124. Kuzawa CW (1998) Adipose tissue in human infancy and childhood: an evolutionary perspective. Am J Phys Anthropol 41:177–209Google Scholar
  125. Kuzawa CW (2007) Developmental origins of life history: growth, productivity, and reproduction. Am J Hum Biol 19:654–661PubMedGoogle Scholar
  126. Lakatos A, Derbeneva O, Younes D, Keator D, Bakken T, Lvova M, Brandon M, Guffanti G, Reglodi D, Saykin A, Weiner M, Macciardi F, Schork N, Wallace DC, Potkin SG, Alzheimer’s Disease Neuroimaging Initiative (2010) Association between mitochondrial DNA variations and Alzheimer’s disease in the ADNI cohort. Neurobiol Aging 31:1355–1363PubMedCentralPubMedGoogle Scholar
  127. Lee AG (2001) Myelin: delivery by raft. Curr Biol 11:R60–R62PubMedGoogle Scholar
  128. Lemere CA, Beierschmitt A, Iglesias M, Spooner ET, Bloom JK, Leverone JF, Zheng JB, Seabrook TJ, Louard D, Li D, Selkoe DJ, Palmour RM, Ervin FR (2004) Alzheimer’s disease Aβ vaccine reduces central nervous system Aβ levels in a non-human primate, the Caribbean vervet. Am J Pathol 165:283–297PubMedCentralPubMedGoogle Scholar
  129. Lemere CA, Oh J, Stanish HA, Peng Y, Pepivani I, Fagan AM, Yamaguchi H, Westmoreland SV, Mansfield KG (2008) Cerebral amyloid-beta protein accumulation with aging in cotton-top tamarins: a model of early Alzheimer’s disease? Rejuven Res 11:321–332Google Scholar
  130. Leonard WR, Robertson ML (1994) Evolutionary perspectives on human nutrition: the influence of brain and body size on diet and metabolism. Am J Hum Biol 6:77–88Google Scholar
  131. Leveille PJ, McGinnis JF, Maxwell DS, de Vellis J (1980) Immunocytochemical localization of glycerol-3-phosphate dehydrogenase in rat oligodendrocytes. Brain Res 196:287–305PubMedGoogle Scholar
  132. Li Z, Okamoto K-I, Hayashi Y, Sheng M (2004) The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119:873–887PubMedGoogle Scholar
  133. Locasale JW, Cantley LC (2011) Metabolic flux and the regulation of mammalian cell growth. Cell Metab 14:443–451PubMedCentralPubMedGoogle Scholar
  134. Lu H, Zou Q, Gu H, Raichle ME, Stein EA, Yang Y (2012) Rat brains also have a default mode network. Proc Natl Acad Sci USA 109:3979–3984PubMedCentralPubMedGoogle Scholar
  135. Lund Madsen P, Hasselbalch SG, Hagemann LP, Skovgaard Olsen K, Bülow J, Holm S, Wildschiødtz G, Paulson OB, Lassen NA (1995) Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation: evidence obtained with the Kety–Schmidt technique. J Cereb Blood Flow Metab 15:485–491Google Scholar
  136. Maeda K, Nwulia E, Chang J, Balkissoon R, Ishizuka K, Chen H, Zandi P, McInnis MG, Sawa A (2006) Differential expression of disrupted-in-schizophrenia (DISC1) in bipolar disorder. Biol Psychiatry 60:929–935PubMedGoogle Scholar
  137. Magistretti PJ (2009) Role of glutamate in neuron-glia metabolic coupling. Am J Clin Nutr 90:875S–880SPubMedGoogle Scholar
  138. Magistretti PJ, Pellerin L, Rothman DL, Shulman RG (1999) Energy on demand. Science 283:496–497PubMedGoogle Scholar
  139. Markus EJ, Petit TL (1987) Neocortical synaptogenesis, aging, and behavior: lifespan development in the motor-sensory system of the rat. Exp Neurol 96:262–278PubMedGoogle Scholar
  140. Mattson MP, Duan W, Maswood N (2002) How does the brain control lifespan? Ageing Res Rev 1:155–165PubMedGoogle Scholar
  141. Miller DJ, Duka T, Stimpson CD, Schapiro SJ, Baze WB, McArthur MJ, Fobbs AJ, Sousa AMM, Sestan N, Wildman DE, Lipovich L, Kuzawa CW, Hof PR, Sherwood CC (2012) Prolonged myelination in human neocortical evolution. Proc Natl Acad Sci USA 109:16480–16485PubMedCentralPubMedGoogle Scholar
  142. Mink JW, Blumenschine RJ, Adams DB (1981) Ratio of central nervous system to body metabolism in vertebrates: its constancy and functional basis. Am J Physiol 241:203–212Google Scholar
  143. Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC (2006) [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology 67:446–452PubMedGoogle Scholar
  144. Mudher A, Lovestone S (2002) Alzheimer’s disease—do tauists and baptists finally shake hands? Trends Neurosci 25:22–26PubMedGoogle Scholar
  145. Mufson EJ, Benzing WC, Cole GM, Wang H, Emerich DF, Sladek JR, Morrison JH, Kordower JH (1994) Apolipoprotein E-immunoreactivity in aged rhesus monkey cortex: colocalization with amyloid plaques. Neurobiol Aging 15:621–627PubMedGoogle Scholar
  146. Myers MG, Olson DP (2012) Central nervous system control of metabolism. Nature 491:357–363PubMedGoogle Scholar
  147. Navarrete A, van Schaik CP, Isler K (2011) Energetics and the evolution of human brain size. Nature 480:91–93PubMedGoogle Scholar
  148. Nehlig A, Pereira de Vasconcelos A (1993) Glucose and ketone body utilization by the brain of neonatal rats. Prog Neurobiol 40:163–221PubMedGoogle Scholar
  149. Nehlig A, Pereira de Vasconcelos A, Boyet S (1988) Quantitative autoradiographic measurement of local cerebral glucose utilization in freely moving rats during postnatal development. J Neurosci 8:2321–2333PubMedGoogle Scholar
  150. Nelson DL, Cox MM (2008) Lehninger principles of biochemistry, 5th edn. W.H. Freeman and Company, New YorkGoogle Scholar
  151. Newington JT, Pitts A, Chien A, Arseneault R, Schubert D, Cumming RC (2011) Amyloid beta resistance in nerve cell lines is mediated by the Warburg effect. PLoS One 6:e19191PubMedCentralPubMedGoogle Scholar
  152. Newman LA, Korol DL, Gold PE (2011) Lactate produced by glycogenolysis in astrocytes regulates memory processing. PLoS One 6:e28427PubMedCentralPubMedGoogle Scholar
  153. Nielsen TH, Bindslev TT, Pedersen SM, Toft P, Olsen NV, Nordström CH (2013) Cerebral energy metabolism during induced mitochondrial dysfunction. Acta Anaesth Scand 57:229–235PubMedGoogle Scholar
  154. Paus T, Zijdenbos A, Worsley K, Collins DL, Blumenthal J, Giedd JN, Rapoport JL, Evans AC (1999) Structural maturation of neural pathways in children and adolescents: in vivo study. Science 283:1908–1911PubMedGoogle Scholar
  155. Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci USA 91:10625–10629PubMedCentralPubMedGoogle Scholar
  156. Pellerin L, Magistretti PJ (2003) Food for thought: challenging the dogmas. J Cereb Blood Flow Metab 23:1282–1286PubMedGoogle Scholar
  157. Perez de Heredia F, Wood IS, Trayhurn P (2010) Hypoxia stimulates lactate release and modulates monocarboxylate transporter (MCT1, MCT2, and MCT4) expression in human adipocytes. Eur J Physiol 459:509–518Google Scholar
  158. Perez SE, Raghanti MA, Hof PR, Kramer L, Ikonomovic MD, Lacor PN, Erwin JM, Sherwood CC, Mufson EJ (2013) Alzheimer’s disease pathology in the neocortex and hippocampus of the western lowland gorilla (Gorilla gorilla gorilla). J Comp NeurolGoogle Scholar
  159. Petanjek Z, Judaš M, Šimic G, Rašin MR, Uylings HBM, Rakic P, Kostović I (2011) Extraordinary neoteny of synaptic spines in the human prefrontal cortex. Proc Natl Acad Sci USA 108:13281–13286PubMedCentralPubMedGoogle Scholar
  160. Peters A, Sethares C, Luebke JI (2008) Synapses are lost during aging in the primate prefrontal cortex. Neuroscience 152:970–981PubMedCentralPubMedGoogle Scholar
  161. Pierron D, Wildman DE, Hüttemann M, Markondapatnaikuni GC, Aras S, Grossman LI (2011) Cytochrome c oxidase: evolution of control via nuclear subunit addition. Biochim Biophys Acta 1817:590–597PubMedCentralPubMedGoogle Scholar
  162. Poduri A, Gearing M, Rebeck GW, Mirra SS, Tigges J, Hyman BT (1994) Apolipoprotein E4 and beta amyloid in senile plaques and cerebral blood vessels of aged rhesus monkeys. Am J Pathol 144:1183–1187PubMedCentralPubMedGoogle Scholar
  163. Powers WJ, Rosenbaum JL, Dence CS, Markham J, Videen TO (1998) Cerebral glucose transport and metabolism in preterm human infants. J Cereb Blood Flow Metab 18:632–638PubMedGoogle Scholar
  164. Preuss TM (2011) The human brain: rewired and running hot. Ann N Y Acad Sci 1225:E182–E191PubMedCentralPubMedGoogle Scholar
  165. Preuss TM, Cáceres M, Oldham MC, Geschwind DH (2004) Human brain evolution: insights from microarrays. Nat Rev Genet 5:850–860PubMedGoogle Scholar
  166. Purves WK, Sadava D, Orians GH (2001) Life: the science of biology, 6th edn. Sinauer Associates, SunderlandGoogle Scholar
  167. Pysh JJ (1970) Mitochondrial changes in rat inferior colliculus during postnatal development: an electron microscopic study. Brain Res 18:325–342PubMedGoogle Scholar
  168. Raichle ME (2006) The brain’s dark energy. Science 314:1249–1250PubMedGoogle Scholar
  169. Raichle ME (2010) Two views of brain function. Trends Cogn Sci 14:180–190PubMedGoogle Scholar
  170. Raichle ME, Snyder AZ (2007) A default mode of brain function: a brief history of an evolving idea. Neuroimage 37:1083–1090PubMedGoogle Scholar
  171. Raichle ME, Posner JB, Plum F (1970) Cerebral blood flow during and after hyperventilation. Arch Neurol 23:394–403PubMedGoogle Scholar
  172. Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL (2001) A default mode of brain function. Proc Natl Acad Sci USA 98:676–682PubMedCentralPubMedGoogle Scholar
  173. Rakic P (2002) Neurogenesis in adult primate neocortex: an evaluation of the evidence. Nat Rev Neurosci 3:65–71PubMedGoogle Scholar
  174. Rakic P, Bourgeois JP, Eckenhoff MF, Zecevic N, Goldman-Rakic PS (1986) Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science 232:232–235PubMedGoogle Scholar
  175. Ramadori G, Coppari R (2011) Does hypothalamic SIRT1 regulate aging? Aging 3:325–328PubMedCentralPubMedGoogle Scholar
  176. Rapoport SI, Horwitz B, Haxby JV, Grady CL (1986) Alzheimer’s disease: metabolic uncoupling of associative brain regions. Can J Neurol Sci 13:540–545PubMedGoogle Scholar
  177. Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, Thibodeau SN, Osborne D (1996) Preclinical evidence of Alzheimer’s disease in persons homozygous for the ε4 allele for apolipoprotein E. N Engl J Med 334:752–758PubMedGoogle Scholar
  178. Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, Saunders AM, Hardy J (2005) Correlations between apolipoprotein E ε4 gene dose and brain-imaging measurements of regional hypometabolism. Proc Natl Acad Sci USA 102:8299–8302PubMedCentralPubMedGoogle Scholar
  179. Rilling JK, Barks SK, Parr LA, Preuss TM, Faber TL, Pagnoni G, Bremner JD, Votaw JR (2007) A comparison of resting-state brain activity in humans and chimpanzees. Proc Natl Acad Sci USA 104:17146–17151PubMedCentralPubMedGoogle Scholar
  180. Rinholm JE, Hamilton NB, Kessaris N, Richardson WD, Bergersen LH, Attwell D (2011) Regulation of oligodendrocyte development and myelination by glucose and lactate. J Neurosci 31:538–548PubMedCentralPubMedGoogle Scholar
  181. Robson SL, Wood B (2008) Hominin life history: reconstruction and evolution. J Anat 212:394–425PubMedCentralPubMedGoogle Scholar
  182. Rosen RF, Farberg AS, Gearing M, Dooyema J, Long PM, Anderson DC, Davis-Turak J, Coppola G, Geschwind DH, Paré J-F, Duong TQ, Hopkins WD, Preuss TM, Walker LC (2008) Tauopathy with paired helical filaments in an aged chimpanzee. J Comp Neurol 509:259–270PubMedCentralPubMedGoogle Scholar
  183. Salthouse TA (2009) When does age-related cognitive decline begin? Neurobiol Aging 30:507–514PubMedCentralPubMedGoogle Scholar
  184. Sánchez-Abarca LI, Tabernero A, Medina JM (2001) Oligodendrocytes use lactate as a source of energy and as a precursor of lipids. Glia 36:321–329PubMedGoogle Scholar
  185. Schmidt TR, Wildman DE, Uddin M, Opazo JC, Goodman M, Grossman LI (2005) Rapid electrostatic evolution at the binding site for cytochrome c on cytochrome c oxidase in anthropoid primates. Proc Natl Acad Sci USA 102:6379–6384PubMedCentralPubMedGoogle Scholar
  186. Schnaider Beeri M, Haroutunian V, Schmeidler J, Sano M, Fam P, Kavanaugh A, Barr AM, Honer WG, Katsel P (2012) Synaptic protein deficits are associated with dementia irrespective of extreme old age. Neurobiol Aging 33:1125.e1–1125.e8Google Scholar
  187. Selkoe DJ (2000) The origins of Alzheimer disease: a is for amyloid. JAMA 283:1615–1617PubMedGoogle Scholar
  188. Semendeferi K, Teffer K, Buxhoeveden DP, Park MS, Bludau S, Amunts K, Travis K, Buckwalter J (2011) Spatial organization of neurons in the frontal pole sets humans apart from great apes. Cereb Cortex 21:1485–1497PubMedGoogle Scholar
  189. Settergren G, Lindblad BS, Persson B (1976) Cerebral blood flow and exchange of oxygen, glucose, ketone bodies, lactate, pyruvate and amino acids in infants. Acta Paediatr Scand 65:343–353PubMedGoogle Scholar
  190. Shaw P, Kabani NJ, Lerch JP, Eckstrand K, Lenroot R, Gogtay N, Greenstein D, Clasen L, Evans A, Rapoport JL, Giedd JN, Wise SP (2008) Neurodevelopmental trajectories of the human cerebral cortex. J Neurosci 28:3586–3594PubMedGoogle Scholar
  191. Sheng M, Hoogenraad CC (2007) The postsynaptic architecture of excitatory synapses: a more quantitative view. Annu Rev Biochem 76:823–847PubMedGoogle Scholar
  192. Sherwood CC, Gordon AD, Allen JS, Phillips KA, Erwin JM, Hof PR, Hopkins WD (2011) Aging of the cerebral cortex differs between humans and chimpanzees. Proc Natl Acad Sci USA 108:13029–13034PubMedCentralPubMedGoogle Scholar
  193. Silva DFF, Esteves AR, Oliveira CR, Cardoso SM (2011) Mitochondria: the common upstream driver of amyloid-β and tau pathology in Alzheimer’s disease. Curr Alzheimer Res 8:563–572PubMedGoogle Scholar
  194. Small GW, Ercoli LM, Silverman DH, Huang SC, Komo S, Bookheimer SY, Lavretsky H, Miller K, Siddarth P, Rasgon NL, Mazziotta JC, Saxena S, Wu HM, Mega MS, Cummings JL, Saunders AM, Pericak-Vance MA, Roses AD, Barrio JR, Phelps ME (2000) Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer’s disease. Proc Natl Acad Sci USA 97:6037–6042PubMedCentralPubMedGoogle Scholar
  195. Smith ME (1973) A regional survey of myelin development: some compositional and metabolic aspects. J Lipid Res 14:541–551PubMedGoogle Scholar
  196. Soane L, Kahraman S, Kristian T, Fiskum G (2007) Mechanisms of impaired mitochondrial energy metabolism in acute and chronic neurodegenerative disorders. J Neurosci Res 85:3407–3415PubMedCentralPubMedGoogle Scholar
  197. Sokoloff L, Mangold R, Wechsler RL, Kennedy C, Kety SS (1955) The effect of mental arithmetic on cerebral circulation and metabolism. J Clin Invest 34:1101–1108PubMedCentralPubMedGoogle Scholar
  198. Somel M, Franz H, Yan Z, Lorenc A, Guo S, Giger T, Kelso J, Nickel B, Dannemann M, Bahn S, Webster MJ, Weickert CS, Lachmann M, Pääbo S, Khaitovich P (2009) Transcriptional neoteny in the human brain. Proc Natl Acad Sci USA 106:5743–5748PubMedCentralPubMedGoogle Scholar
  199. Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW (2003) Mapping cortical change across the human life span. Nat Neurosci 6:309–315PubMedGoogle Scholar
  200. Spocter MA, Hopkins WD, Barks SK, Bianchi S, Hehmeyer AE, Anderson SM, Stimpson CD, Fobbs AJ, Hof PR, Sherwood CC (2012) Neuropil distribution in the cerebral cortex differs between humans and chimpanzees. J Comp Neurol 520:2917–2929PubMedCentralPubMedGoogle Scholar
  201. Spreng RN, Mar RA, Kim ASN (2009) The common neural basis of autobiographical memory, prospection, navigation, theory of mind, and the default mode: a quantitative meta-analysis. J Cogn Neurosci 21:489–510PubMedGoogle Scholar
  202. Star EN, Kwiatkowski DJ, Murthy VN (2002) Rapid turnover of actin in dendritic spines and its regulation by activity. Nat Neurosci 5:239–246PubMedGoogle Scholar
  203. Sterner KN, McGowen MR, Chugani HT, Tarca AL, Sherwood CC, Hof PR, Kuzawa CW, Boddy AM, Raaum RL, Weckle A, Lipovich L, Grossman LI, Uddin M, Goodman M, Wildman DE (2013) Characterization of human cortical gene expression in relation to glucose utilization. Am J Hum Biol 25:418–430PubMedGoogle Scholar
  204. Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM (2011) Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144:810–823PubMedCentralPubMedGoogle Scholar
  205. Syner FN, Goodman M (1966) Differences in the lactic dehydrogenases of primate brains. Nature 209:426–428PubMedGoogle Scholar
  206. Teffer K, Semendeferi K (2012) Human prefrontal cortex: evolution, development, and pathology. In: Hofman MA, Falk D (eds) Evolution of the primate brain: from neuron to behavior. Progress in brain research, vol 195. Elsevier, New York, pp 191–218Google Scholar
  207. Tekkök SB, Brown AM, Westenbroek R, Pellerin L, Ransom BR (2005) Transfer of glycogen-derived lactate from astrocytes to axons via specific monocarboxylate transporters supports mouse optic nerve activity. J Neurosci Res 81:644–652PubMedGoogle Scholar
  208. Tower DB (1954) Structural and functional organization of mammalian cerebral cortex: the correlation of neurone density with brain size. J Comp Neurol 101:19–52PubMedGoogle Scholar
  209. Travis K, Ford K, Jacobs B (2005) Regional dendritic variation in neonatal human cortex: a quantitative Golgi study. Dev Neurosci 27:277–287PubMedGoogle Scholar
  210. Trushina E, Nemutlu E, Zhang S, Christensen T, Camp J, Mesa J, Siddiqui A, Tamura Y, Sesaki H, Wengenack TM, Dzeja PP, Poduslo JF (2012) Defects in mitochondrial dynamics and metabolomic signatures of evolving energetic stress in mouse models of familial Alzheimer’s disease. PLoS One 7:e32737PubMedCentralPubMedGoogle Scholar
  211. Uddin M, Wildman DE, Liu G, Xu W, Johnson RM, Hof PR, Kapatos G, Grossman LI, Goodman M (2004) Sister grouping of chimpanzees and humans as revealed by genome-wide phylogenetic analysis of brain gene expression profiles. Proc Natl Acad Sci USA 101:2957–2962PubMedCentralPubMedGoogle Scholar
  212. Uddin M, Opazo JC, Wildman DE, Sherwood CC, Hof PR, Goodman M, Grossman LI (2008) Molecular evolution of the cytochrome c oxidase subunit 5A gene in primates. BMC Evol Biol 8:8PubMedCentralPubMedGoogle Scholar
  213. Ullah MS, Davies AJ, Halestrap AP (2006) The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1alpha-dependent mechanism. J Biol Chem 281:9030–9037PubMedGoogle Scholar
  214. Uylings HBM, de Brabander JM (2002) Neuronal changes in normal human aging and Alzheimer’s disease. Brain Cogn 49:268–276PubMedGoogle Scholar
  215. Vaishnavi SN, Vlassenko AG, Rundle MM, Snyder AZ, Mintun MA, Raichle ME (2010) Regional aerobic glycolysis in the human brain. Proc Natl Acad Sci USA 107:17757–17762PubMedCentralPubMedGoogle Scholar
  216. Valla J, Berndt JD, Gonzalez-Lima F (2001) Energy hypometabolism in posterior cingulate cortex of Alzheimer’s patients: superficial laminar cytochrome oxidase associated with disease duration. J Neurosci 21:4923–4930PubMedGoogle Scholar
  217. Valla J, Yaari R, Wolf AB, Kusne Y, Beach TG, Roher AE, Corneveaux JJ, Huentelman MJ, Caselli RJ, Reiman EM (2010) Reduced posterior cingulate mitochondrial activity in expired young adult carriers of the APOE ε4 allele, the major late-onset Alzheimer’s susceptibility gene. J Alzheimers Dis 22:307–313PubMedCentralPubMedGoogle Scholar
  218. Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–1033PubMedCentralPubMedGoogle Scholar
  219. Vander Heiden MG, Locasale JW, Swanson KD, Sharfi H (2010) Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 329:1492–1499PubMedGoogle Scholar
  220. Vaughn AE, Deshmukh M (2008) Glucose metabolism inhibits apoptosis in neurons and cancer cells by redox inactivation of cytochrome c. Nature 10:1477–1483Google Scholar
  221. Vincent JL, Snyder AZ, Fox MD, Shannon BJ, Andrews JR, Raichle ME, Buckner RL (2006) Coherent spontaneous activity identifies a hippocampal-parietal memory network. J Neurophysiol 96:3517–3531PubMedGoogle Scholar
  222. Vincent JL, Patel GH, Fox MD, Snyder AZ, Baker JT, Van Essen DC, Zempel JM, Snyder LH, Corbetta M, Raichle ME (2007) Intrinsic functional architecture in the anaesthetized monkey brain. Nature 447:83–86PubMedGoogle Scholar
  223. Vlassenko AG, Rundle MM, Raichle ME, Mintun MA (2006) Regulation of blood flow in activated human brain by cytosolic NADH/NAD+ ratio. Proc Natl Acad Sci USA 103:1964–1969PubMedCentralPubMedGoogle Scholar
  224. Vlassenko AG, Vaishnavi SN, Couture L, Sacco D, Shannon BJ, Mach RH, Morris JC, Raichle ME, Mintun MA (2010) Spatial correlation between brain aerobic glycolysis and amyloid-β (Aβ) deposition. Proc Natl Acad Sci USA 107:17763–17767PubMedCentralPubMedGoogle Scholar
  225. Walker LC, Cork LC (1999) The neurobiology of aging in nonhuman primates. In: Terry RD, Katzman R, Bick KL, Sisodia SS (eds) Alzheimer disease, 2nd edn. Lippincott, Williams, and Wilkins, Philadelphia, pp 233–243Google Scholar
  226. Walker LC, Kitt CA, Schwam E, Buckwald B, Garcia F, Sepinwall J, Price DL (1987) Senile plaques in aged squirrel monkeys. Neurobiol Aging 8:291–296PubMedGoogle Scholar
  227. Wang X, Michaelis ML, Michaelis EK (2010) Functional genomics of brain aging and Alzheimer’s disease: focus on selective neuronal vulnerability. Curr Genomics 11:618–633PubMedCentralPubMedGoogle Scholar
  228. Warburg O (1956) On the origin of cancer cells. Science 123:309–314PubMedGoogle Scholar
  229. Warburg O, Posener K, Negelein E (1924) Über den Stoffwechsel der Carcinomzelle. Biochem Z 152:309–344Google Scholar
  230. Warburg O, Wind F, Negelein E (1927) The metabolism of tumors in the body. J Gen Physiol 8:519–530PubMedCentralPubMedGoogle Scholar
  231. Wolkow CA, Kimura KD, Lee MS, Ruvkun G (2000) Regulation of C. elegans life-span by insulin like signaling in the nervous system. Science 290:147–150PubMedGoogle Scholar
  232. Wyss MT, Jolivet R, Buck A, Magistretti PJ, Weber B (2011) In vivo evidence for lactate as a neuronal energy source. J Neurosci 31:7477–7485PubMedGoogle Scholar
  233. Yakovlev PI, Lecours A (1967) The myelogenetic cycles of regional maturation of the brain. In: Minkowski A (ed) Regional development of the brain in early life. Blackwell Science, Oxford, pp 3–70Google Scholar
  234. Yang Y, Mufson EJ, Herrup K (2003) Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer’s disease. J Neurosci 23:2557–2563PubMedGoogle Scholar
  235. Yi JJ, Ehlers MD (2005) Ubiquitin and protein turnover in synapse function. Neuron 47:629–632PubMedGoogle Scholar
  236. Zala D, Hinckelmann M-V, Yu H, Lyra da Cunha MM, Liot G, Cordelières FP, Marco S, Saudou F (2013) Vesicular glycolysis provides on-board energy for fast axonal transport. Cell 152:479–491PubMedGoogle Scholar
  237. Zivraj KH, Tung YCL, Piper M, Gumy L, Fawcett JW, Yeo GSH, Holt CE (2010) Subcellular profiling reveals distinct and developmentally regulated repertoire of growth cone mRNAs. J Neurosci 30:15464–15478PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Amy L. Bauernfeind
    • 1
  • Sarah K. Barks
    • 1
  • Tetyana Duka
    • 1
  • Lawrence I. Grossman
    • 2
  • Patrick R. Hof
    • 3
    • 4
  • Chet C. Sherwood
    • 1
  1. 1.Department of AnthropologyThe George Washington UniversityWashingtonUSA
  2. 2.Center for Molecular Medicine and GeneticsWayne State University School of MedicineDetroitUSA
  3. 3.Fishberg Department of Neuroscience, Friedman Brain InstituteIcahn School of Medicine at Mount SinaiNew YorkUSA
  4. 4.New York Consortium in Evolutionary PrimatologyNew YorkUSA

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