Advertisement

Drugs & Aging

, Volume 6, Issue 3, pp 210–218 | Cite as

Age-Related Changes in Cerebral Oxidative Metabolism

Implications for Drug Therapy
  • Siegfried Hoyer
Physiological Aspects of Aging

Summary

Glucose metabolism in the brain is of central significance. It contributes to the synthesis of the neurotransmitters acetylcholine, glutamate, aspartate, γ-aminobutyric acid (GABA) and glycine, and yields adenosine triphosphate (ATP) as the driving force of almost all cellular and molecular work. Neuronal glucose metabolism is controlled antagonistically by insulin and cortisol via amplification and desensitisation of the insulin signal from the insulin receptor. Normal aging of mammalian brains is associated with numerous inherent metabolic changes. The metabolic changes that are of pivotal importance include probable primary inherent variations in the neuronal insulin receptor, the desensitisation of the neuronal insulin receptor by circulating cortisol and receptor dysfunction subsequent to changes in membrane structure and function.

As a consequence, slight aberrations in glucose/energy metabolism become obvious under resting conditions, indicating incipient variations of neuronal homeostasis as a common path in the aging process. Subsequent to the changes in glucose metabolism and energy production, variations occur in acetylcholine synthesis and release, extracellular concentration and receptor binding of glutamate and cytosolic Ca++ homeostasis. Additionally, free radical formation and membrane structure changes must be considered as primary changes during aging. Stressful events occurring more frequently during aging aggravate and prolong these changes that are accompanied by membrane lability.

There is increasing evidence that the sum of these metabolic variations develops in a self-propagating manner, following the principle of self-organised criticality. The progress from one metalabile steady state into another by additionally occurring events of small quantity may lead to increasing neuronal damage. As yet, there is no rational basis for any drug treatment to influence the process of normal cerebral aging. However, there is a reasonable basis for the assumption that long term mental activation contributes to the maintenance of mental capacity in old age.

Keywords

Insulin Receptor Acetylcholine Synthesis Energy Pool Cerebral Oxidative Metabolism Neuronal Insulin Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Gibbs EL, Lennox WG, Nims LF, et al. Arterial and cerebral venous blood: arterial-venous differences in man. J Biol Chem 1942; 144: 325–32Google Scholar
  2. 2.
    Gottstein U, Bernsmeier A, Sedlmeyer I. Der Kohlenhydrat-stoffwechsel des menschlichen Gehirns, I: Untersuchungen mit substratspezifischen enzymatischen Methoden bei normaler Hirndurchblutung. Klin Wschr 1963; 41: 943–8PubMedGoogle Scholar
  3. 3.
    Hoyer S. Der Aminosäurenstoffwechsel des normalen menschlichen Gehirns. Klin Wschr 1970; 48: 1239–43PubMedGoogle Scholar
  4. 4.
    Siesjö BK. Brain energy metabolism. Chichester: Wiley, 1978: 1–28, 151–209Google Scholar
  5. 5.
    Goldstein BJ. Regulation of insulin receptor signalling by protein-tyrosine dephosphorylation. Receptor 1993; 3: 1–15PubMedGoogle Scholar
  6. 6.
    Häring HU. The insulin receptor: signalling mechanism and contribution to the pathogenesis of insulin resistance. Diabetologia 1991; 34: 848–61PubMedGoogle Scholar
  7. 7.
    Roth RA, Beaudoin J. Phosphorylation of purified insulin receptor by cAMP kinase. Diabetes 1987; 36: 123–6PubMedGoogle Scholar
  8. 8.
    Häring HU, Kirsch D, Obermaier B, et al. Decreased tyrosine kinase activity of insulin receptor isolated from rat adipocytes rendered insulin-resistant by catecholamine treatment in vitro. Biochem J 1986; 234: 59–66PubMedGoogle Scholar
  9. 9.
    Giorgino F, Almahfouz A, Goodyear LJ, et al. Glucocorticoid regulation of insulin receptor and substrate IRS-1 tyrosine phosphorylation in rat skeletal muscle in vivo. J Clin Invest 1993; 91: 2020–30PubMedGoogle Scholar
  10. 10.
    Turnbow MA, Keller SR, Rice KM, et al. Dexamethasone down-regulation of insulin receptor substrate-1 in 3T3-L1 adipocytes. J Biol Chem 1994; 269: 2516–20PubMedGoogle Scholar
  11. 11.
    LeRoith D, Shemer J, Adamo M, et al. Insulin and IGF-I stimulate phosphorylation of their respective receptors in intact neuronal and glial cells in primary culture. J Mol Neurosci 1989; 1: 3–8PubMedGoogle Scholar
  12. 12.
    Unger JW, Livinston JN, Moss AM. Insulin receptors in the central nervous system: localization, signalling mechanisms and functional aspects. Progr Neurobiol 1991; 36: 343–62Google Scholar
  13. 13.
    Devaskar SU, Giddings SJ, Rajakumar PA, et al. Insulin gene expression and insulin synthesis in mammalian neuronal cells. J Biol Chem 1994; 269: 8445–54PubMedGoogle Scholar
  14. 14.
    Hill JM, Lesniak MA, Pert CB, et al. Autoradiographic localization of insulin receptors in rat brain: prominence in olfactory and limbic areas. Neuroscience 1986; 17: 1127–38PubMedGoogle Scholar
  15. 15.
    Baskin DG, Schwartz MW, Sipols AJ, et al. Insulin receptor substrate-1 (IRS-1) expression in rat brain. Endocrinology 1994; 134: 1952–5PubMedGoogle Scholar
  16. 16.
    Bachelard HS. Specific and kinetic properties of monosaccharide uptake into guinea pig cerebral cortex in vitro. J Neurochem 1971; 13: 213–22Google Scholar
  17. 17.
    Hertz MM, Paulson OB, Barry DL, et al. Insulin increases glucose transfer across the blood-brain barrier. J Clin Invest 1981; 67: 597–604PubMedGoogle Scholar
  18. 18.
    Kahn CR. The molecular mechanism of insulin action. Ann Rev Med 1985; 36: 429–51PubMedGoogle Scholar
  19. 19.
    Pardridge WM, Boado RJ, Farrell CR. Brain-type glucose transporter (GLUT-1) is selectively localized to the blood-brain barrier. J Biol Chem 1990; 265: 18035–40PubMedGoogle Scholar
  20. 20.
    Newsholme EA, Start C. Regulation in metabolism. Chichester: Wiley, 1973: 88–145Google Scholar
  21. 21.
    Garland PB, Randle PJ. Control of pyruvate dehydrogenase in the perfused rat heart by the intracellular concentration of acetyl-coenzyme A. Biochem J 1964; 91: 76C-77CGoogle Scholar
  22. 22.
    Perry EK, Perry RH, Tomlinson BE, et al. Coenzyme A acetylating enzymes in Alzheimer’s disease: possible cholinergic ‘compartment’ of pyruvate dehydrogenase. Neurosci Lett 1980; 18: 105–10PubMedGoogle Scholar
  23. 23.
    Linn TC, Pettit FH, Reed LJ. Alpha-keto acid dehydrogenase complexes, X: regulation of the activity of the pyruvate dehydrogenase complex from beef kidney mitochondria by phosphorylation and dephosphorylation. Proc Natl Acad Sci USA 1969; 62: 234–41PubMedGoogle Scholar
  24. 24.
    Linn TC, Pettit FH, Hucho F, et al. Alpha-keto acid dehydrogenase complexes, XI: comparative studies of regulatory properties of the pyruvate dehydrogenase complex from kidney, heart, and liver mitochondria. Proc Natl Acad Sci USA 1969; 64: 227–34PubMedGoogle Scholar
  25. 25.
    Browning M, Baudry M, Bennett WF, et al. Phosphorylation-mediated changes in pyruvate dehydrogenase activity influence pyruvate-supported calcium accumulation by brain mitochondria. J Neurochem 1981; 36: 1932–40PubMedGoogle Scholar
  26. 26.
    Hansford RG, Castro F. Role of CA2+ in pyruvate dehydrogenase interconversion in brain mitochondria and synaptosomes. Biochem J 1985; 227: 129–36PubMedGoogle Scholar
  27. 27.
    Baudry M, Fuchs J, Kessler M, et al. Entorhinal cortex lesions induce a decreased calcium transport in hippocampal mitochondria. Science 1982; 216: 411–3PubMedGoogle Scholar
  28. 28.
    Garland PB, Newsholme EA, Randle PJ. Regulation of glucose uptake by muscle, 9: effects of fatty acids and ketone bodies, and of alloxan-diabetes and starvation, on pyruvate metabolism and on lactate/pyruvate and L-glycerol 3-phosphate/dihydroacetone phosphate concentration ratios in the rat heart and rat diaphragm muscles. Biochem J 1964; 93: 665–78PubMedGoogle Scholar
  29. 29.
    Hoyer S, Prem L, Sorbi S, et al. Stimulation of glycolytic key enzymes in cerebral cortex by insulin. NeuroReport 1993; 4: 991–3PubMedGoogle Scholar
  30. 30.
    Jope R, Blass JP. The regulation of pyruvate dehyd rogenase in brain in vivo. J Neurochem 1976; 26: 709–14PubMedGoogle Scholar
  31. 31.
    Denton RM, McCormack JG, Thomas AP. Hormonal regulation of intramitochondrial metabolism. Biol Chem Hoppe-Seyler 1986; 367 (Suppl.): 64Google Scholar
  32. 32.
    Kryiakis JM, Hausman RE, Peterson SW. Insulin stimulates choline acetyltransferase activity in cultured embryonic chicken retina neurons. Proc Natl Acad Sci USA 1987; 84: 7463–7Google Scholar
  33. 33.
    Henneberg N, Hoyer S. Short-term or long-term intracerebroventricular (i.c.v.) infusion of insulin exhibits a discrete anabolic effect on cerebral energy metabolism in the rat. Neurosci Lett 1994; 175: 153–6PubMedGoogle Scholar
  34. 34.
    Sacks W. Cerebral metabolism of isotopic glucose in normal human subjects. J Appl Physiol 1957; 10: 37–44PubMedGoogle Scholar
  35. 35.
    Sacks W. Cerebral metabolism of doubly labelled glucose in human in vivo. J Appl Physiol 1965; 20: 117–30PubMedGoogle Scholar
  36. 36.
    Wong KL, Tyce GM. Glucose and amino acid metabolism in rat brain during sustained hypoglycemia. Neurochem Res 1983: 8: 401–15PubMedGoogle Scholar
  37. 37.
    Strange PG. The structure and mechanism of neurotransmitter receptors: implications for the structure and function of the central nervous system. Biochem J 1988; 249: 309–18PubMedGoogle Scholar
  38. 38.
    Walaas I, Fonnum F. Biochemical evidence for glutamate as a transmitter in hippocampal efferents to the basal forebrain and hypothalamus in the rat brain. Neuroscience 1980; 5: 1691–8PubMedGoogle Scholar
  39. 39.
    Davies SW, McBean GJ, Roberts PJ. A glutamatergic innervation of the nucleus basalis/substantia innominata. Neurosci Lett 1984; 45: 105–10PubMedGoogle Scholar
  40. 40.
    Smith CCT, Bowen DM, Davison AN. The evoked release of endogenous amino acids from tissue prisms of human neocortex. Brain Res 1983; 269: 103–9PubMedGoogle Scholar
  41. 41.
    Rothman SM, Olney JW. Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann Neurol 1986; 19: 105–11PubMedGoogle Scholar
  42. 42.
    Drejer J, Honore T, Schousboe A. Excitatory amino acid-induced release of 3H-GABA from cultured mouse cerebral cortex interneurons. J Neurosci 1987; 7: 2910–6PubMedGoogle Scholar
  43. 43.
    Stelzer A, Wong RKS. GABAa responses in hippocampal neurons are potentiated by glutamate. Nature 1989; 337: 170–3PubMedGoogle Scholar
  44. 44.
    Hoyer S. Senile dementia and Alzheimer’s disease. Brain blood flow and metabolism. Prog Neuropsychopharmacol Biol Psychiatr 1986; 10: 447–78Google Scholar
  45. 45.
    Meier-Ruge W, Hunziker O, Iwangoff P, et al. Effect of age on morphological and biochemical parameters of the human brain. In: Stein DC, editor. The psychobiology of aging: problems and perspectives. Amsterdam: North-Holland, 1980: 297–17Google Scholar
  46. 46.
    Davies P. Neurotransmitter-related enzymes in senile dementia of the Alzheimer type. Brain Res 1979; 171: 319–27PubMedGoogle Scholar
  47. 47.
    Bowen DM, Smith CB, White P, et al. Chemical pathology of the organic dementias, II: quantitative estimation of cellular changes in postmortem brain. Brain 1977; 100: 427–53PubMedGoogle Scholar
  48. 48.
    London ED, Nespor SM, Ohata M, et al. Local cerebral glucose utilization during development and aging in the Fischer-344 rat. J Neurochem 1981; 37: 217–21PubMedGoogle Scholar
  49. 49.
    Smith CB, Goochee C, Rapoport I, et al. Effects of aging on local rates of cerebral glucose utilization in the rat. Brain 1980; 103: 351–65PubMedGoogle Scholar
  50. 50.
    Takei H, Fredericks WR, London ED, et al. Cerebral blood flow and oxidative metabolism in conscious Fischer-344 rats of different ages. J Neurochem 1983; 40: 801–5PubMedGoogle Scholar
  51. 51.
    Hoyer S. The effect of age on glucose and energy metabolism in brain cortex of rats. Arch Gerontol Geriatr 1985; 4: 193–203PubMedGoogle Scholar
  52. 52.
    Iwangoff P, Armbruster R, Enz A, et al. Glycolytic enzymes from human autoptic brain cortex: Normally aged and demented cases. In: Roberts PJ, editor. Biochemistry of dementia. Chichester: Wiley, 1980: 258–62Google Scholar
  53. 53.
    Leong SW, Clark JB. Regional enzyme development in rat brain. Enzymes associated with glucose utilization. Biochem J 1984; 218: 131–8PubMedGoogle Scholar
  54. 54.
    Benzi G, Arrigoni E, Dagani F, et al. Aging and brain enzymes. In: Barbagello-Sangiorgi G, Exton-Smith AN, editors. The aging brain: neurological and mental disturbances. New York: Plenum Press, 1980: 1–13Google Scholar
  55. 55.
    Leong SF, Lim JCK, Clark JB. Energy-metabolizing enzymes in brain regions of adult and aging rats. J Neurochem 1981; 37: 1548–56PubMedGoogle Scholar
  56. 56.
    Deshmukh DR, Owen OE, Patel MS. Effect of aging on the metabolism of pyruvate and 3-hydroxybutyrate in non-synaptic and synaptic mitochondria from rat brain. J Neurochem 1980; 34: 1219–24PubMedGoogle Scholar
  57. 57.
    Patel MS. Age-dependent changes in the oxidative metabolism in rat brain. J Gerontol 1977; 32: 643–6PubMedGoogle Scholar
  58. 58.
    Sylvia AL, Rosenthal M. The effect of age and lung pathology on cytochrome a, a3 redox levels in rat cerebral cortex. Brain Res 1978; 146: 109–12PubMedGoogle Scholar
  59. 59.
    Peng MT, Peng YL, Chen FN. Age-dependent changes in the oxygen consumption of the cerebral cortex, hypothalamus, hippocampus and amygdaloid in rats. J Gerontol 1977; 32: 517–22PubMedGoogle Scholar
  60. 60.
    Gibson GE, Peterson C. Aging decreases oxidative metabolism and the release and synthesis of acetylcholine. J Neurochem 1981; 37: 978–84PubMedGoogle Scholar
  61. 61.
    Pedata F, Slavikova J, Kotas A, et al. Acetylcholine release from rat cortical slices during postnatal development and aging. Neurobiol Aging 1983; 4: 31–5PubMedGoogle Scholar
  62. 62.
    Dastur DK, Lane MH, Hansen DB, et al. Effects of aging on cerebral circulation and metabolism in man. In: Birren JE, Butler RN, Greenhouse SW, et al., editors. Human aging: a biological and behavioural study. Bethesda, Maryland, US Department of Health, Education and Welfare, National Institute of Mental Health; 1963. DHEW Publication no. 986: 59–76Google Scholar
  63. 63.
    Dastur DK. Cerebral blood flow and metabolism in normal human aging, pathological aging, and senile dementia. J Cereb Blood Flow Metab 1985; 5: 1–9PubMedGoogle Scholar
  64. 64.
    Hoyer S. Oxidative energy metabolism in Alzheimer brain: studies in early-onset and late-onset cases. Mol Chem Neuropathol 1992; 16: 207–24PubMedGoogle Scholar
  65. 65.
    Dutschke K, Nitsch RM, Hoyer S. Short-term mental activation accelerates the age-related decline in brain tissue levels of high-energy phosphates. Arch Gerontol Geriatr 1994; 19: 43–51PubMedGoogle Scholar
  66. 66.
    Benzi G, Pastoris O, Villa RF, et al. Effect of aging on cerebral cortex energy metabolism in hypoglycemia and posthypoglycemic recovery. Neurobiol Aging 1984; 5: 205–12PubMedGoogle Scholar
  67. 67.
    Hoyer S, Krier C. Ischemia and the aging brain. Studies on glucose and energy metabolism in rat cerebral cortex. Neurobiol Aging 1986; 7: 23–9PubMedGoogle Scholar
  68. 68.
    Hoyer S, Betz K. Abnormalities in glucose and energy metabolism are more severe in the hippocampus than in the cerebral cortex in postischemic recovery in aged rats. Neurosci Lett 1988; 94: 167–72PubMedGoogle Scholar
  69. 69.
    Nohl H, Krämer R. Molecular basis of age-dependent changes in the activity of adenine nucleotide translocase. Mech Ageing Develop 1980; 14: 137–44Google Scholar
  70. 70.
    Davies KJA, Goldberg AL. Oxygen radicals stimulate intracellular proteolysis and lipid peroxidation by independent mechanisms in erythrocytes. J Biol Chem 1987; 262: 8220–6PubMedGoogle Scholar
  71. 71.
    Harman D. The aging process. Proc Natl Acad Sci USA 1981; 78: 7124–8PubMedGoogle Scholar
  72. 72.
    Leibovitz BE, Siegel BV. Aspects of free radical reactions in biological systems: aging. J Gerontol 1980; 35: 45–56PubMedGoogle Scholar
  73. 73.
    Scarpa M, Rigo A, Viglino P, et al. Age dependence of the level of the enzymes involved in the protection against active oxygen species in the rat brain. Proc Soc Exp Biol Med 1987; 185: 129–33PubMedGoogle Scholar
  74. 74.
    Rehncrona S, Hauge HN, Siesjö BK. Enhancement of iron-catalyzed free radical formation by acidosis in brain homogenates: difference in effect by lactic acid and CO2. J Cereb Blood Flow Metabol 1989; 9: 65–70Google Scholar
  75. 75.
    Fucci L, Oliver CN, Coon MJ, et al. Inactivation of key metabolic enzymes by mixed-function oxidation reactions: possible implications in protein turnover and ageing. Proc Natl Acad Sci USA 1983; 80: 1521–5PubMedGoogle Scholar
  76. 76.
    Levine RL, Oliver CN, Fulks RM, et al. Turnover of bacterial glutamine synthetase: oxidative inactivation precedes proteolysis. Proc Natl Acad Sci USA 1981; 78: 2120–4PubMedGoogle Scholar
  77. 77.
    Stadtman ER. Protein oxidation and aging. Science 1992; 257: 1220–4PubMedGoogle Scholar
  78. 78.
    Stadtman ER, Berlett BS. Fenton chemistry. Amino acid oxidation. J Biol Chem 1991; 266: 17201–11PubMedGoogle Scholar
  79. 79.
    Stadtman ER, Oliver CN. Metal-catalyzed oxidation of proteins: physiological consequences. J Biol Chem 1991; 266: 2005–8PubMedGoogle Scholar
  80. 80.
    Goldberg AL, Boches FS. Oxidized proteins in erythrocytes are rapidly degraded by the adenosine triphosphate-dependent proteolytic system. Science 1982; 215: 1107–9PubMedGoogle Scholar
  81. 81.
    Okada M, Ishikawa M, Mizushima Y. Identification of a ubiquitin- and ATP-dependent protein degradation pathway in rat cerebral cortex. Biochim Biophys Acta 1991; 1073: 514–20PubMedGoogle Scholar
  82. 82.
    Sawada M, Sester U, Carlson JS. Superoxide radical formation and associated biochemical alterations in the plasma membrane of brain, heart and liver during the lifetime of the rat. J Cell Biochem 1992; 48: 296–04PubMedGoogle Scholar
  83. 83.
    Carney JM, Starke-Reed PE, Oliver CN, et al. Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tertbutyl-alpha-phenylnitrone. Proc Natl Acad Sci USA 1991; 88: 3633–6PubMedGoogle Scholar
  84. 84.
    Smith CD, Carney JM, Starke-Reed PE, et al. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer’s disease. Proc Natl Acad Sci USA 1991; 88: 10540–3PubMedGoogle Scholar
  85. 85.
    Gutteridge JMC, Halliwell B. The measurement and mechanism of lipid peroxidation in biological systems. Trends Biochem Sci 1990; 15: 129–35PubMedGoogle Scholar
  86. 86.
    Söderberg M, Edlund C, Kristensson K, et al. Lipid compositions of different regions of the human brain during aging. J Neurochem 1990; 54: 415–23PubMedGoogle Scholar
  87. 87.
    Svennerholm L, Boström K, Heiander GG, et al. Membrane lipids in aging human brain. J Neurochem 1991; 56: 2051–9PubMedGoogle Scholar
  88. 88.
    Svennerholm L, Boström K, Jungbjer B, et al. Membrane lipids of adult human brain: lipid composition of frontal and temporal lobe in subjects of age 20 to 100 years. J Neurochem 1994; 63: 1802–11PubMedGoogle Scholar
  89. 89.
    Suzuki H, Hayakawa S, Wada S. Effect of age on the modification of brain polyunsaturated fatty acids and enzyme activities by fish oil diet in rats. Mech Ageing Develop 1989; 50: 17–25Google Scholar
  90. 90.
    Benzi G, Pastoris I, Tentoni S, et al. Modifications in cerebral lipid metabolism by severe glucose deprivation during aging. Neurobiol Aging 1987; 8: 457–63PubMedGoogle Scholar
  91. 91.
    Chan PH, Fishman RA. Brain edema: Induction in cortical slices by polyunsaturated fatty acids. Science 1978; 201: 358–60PubMedGoogle Scholar
  92. 92.
    Terracina L, Brunetti M, Avellini L, et al. Arachidonic and palmitic acid utilization in aged rat brain areas. Mol Cell Biochem 1992; 115: 35–42PubMedGoogle Scholar
  93. 93.
    Nadiv O, Cohen O, Zick Y. Defects in insulin’s signal transduction in old rat livers. Endocrinology 1992; 130: 1515–24PubMedGoogle Scholar
  94. 94.
    Nadiv O, Shinitzky M, Manu H, et al. Elevated protein tyrosine phosphatase activity and increased membrane viscosity are associated with impaired activation of the insulin receptor kinase in old rats. Biochem J 1994: 298: 443–50PubMedGoogle Scholar
  95. 95.
    Defronzo RA. Glucose intolerance and aging. Evidence for tissue insensitivity to insulin. Diabetes 1979; 28: 1095–101PubMedGoogle Scholar
  96. 96.
    Perego C, Vetrugno CC, DeSimoni MG, et al. Aging prolongs the stress-induced release of noradrenaline in rat hypothalamus. Neurosci Lett 1993; 157: 127–30PubMedGoogle Scholar
  97. 97.
    Sapolsky RM, Krey LC, McEwen BS. Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response. Proc Natl Acad Sci USA 1984; 81: 6174–7PubMedGoogle Scholar
  98. 98.
    Sapolsky RM, Krey LC, McEwen BS. The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocrine Rev 1986; 7: 284–301Google Scholar
  99. 99.
    Bak P, Tang C, Wiesenfeld K. Self-organized criticality. Physic Rev A 1988; 38: 367–74Google Scholar
  100. 100.
    Held GA, Solina DH, Keane DT, et al. Experimental study of critical-mass fluctuations in an evolving sandpile. Physic Rev Lett 1990; 65: 1120–3Google Scholar
  101. 101.
    Greenough WT. Structural correlates of information storage in the mammalian brain: a review and hypothesis. Trends Neurosci 1984; 7: 229–33Google Scholar
  102. 102.
    Paylor R, Morrison SK, Rudy JW, et al. Brief exposure to an enriched environment improves performance on the Morris water task and increases hippocampal cytosolic protein kinase C activity in young rats. Behav Brain Res 1992; 52: 49–59PubMedGoogle Scholar
  103. 103.
    Lee MK, Graham SN, Gold PE. Memory enhancement with post-training intraventricular glucose injections in rats. Behav Neurosci 1988; 102: 591–5PubMedGoogle Scholar

Copyright information

© Adis International Limited 1995

Authors and Affiliations

  • Siegfried Hoyer
    • 1
  1. 1.Brain Metabolism Group, Department of Pathochemistry and General NeurochemistryUniversity of Heidelberg, Im Neuenheimer Feld 220/221,69120HeidelbergGermany

Personalised recommendations