Skip to main content
SpringerLink
Log in

Pathobiochemische Störungen im oxydativen Hirnstoffwechsel und ihre therapeutische Beeinflußbarkeit

  • Conference paper
Hirnleistungsstörungen im Alter

Zusammenfassung

Lang anhaltende oder bleibende Störungen des oxydativen Hirnstoffwechsels können ausgelöst werden durch eine Reihe unterschiedlicher extrazerebraler Ursachen, die sich klinisch überwiegend als psychologische Defizite und weniger als neurologische Ausfälle nachweisen lassen (Hoyer 1982, 1988 b). Soweit die psychologischen Defizite erworbene intellektuelle Fähigkeiten betreffen, werden sie als Demenz bezeichnet (Jaspers 1959) und bei extrazerebraler Ursache als sekundäre Form klassifiziert. Davon abgegrenzt sind primäre Demenzen, bei denen es sich um authochtone Hirnerkrankungen handelt, die sich in degenerative und vaskuläre Formen gliedern lassen. Primär degenerative Demenzen dominieren gegenüber den primär vaskulären Formen mit etwa zwei Drittel zu einem Drittel (Tomlinson et al. 1970; Jellinger 1976). Bei primär degenerativen Demenzen steht die Demenz vom Alzheimer-Typ im Vordergrund (Tomlinson 1980), die sich aus genetischer, morphologischer, pathobiochemischer und klinischer Sicht in solche mit frühem und solche mit spätem Beginn gliedert (Mann et al. 1984; Bowen u. Davison 1986; Roth 1986; Goate et al. 1989).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 54.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 69.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

Literatur

  • Bachelard HS (1971) Specific and kinetic properties of monosaccharide uptake into guinea pig cerebral cortex in vitro. J Neurochem 13:213–222

    Article  Google Scholar 

  • Barkulis SS, Geiger A, Kawikata Y, Aguilar V (1960) A study of the incorporation of 14C derived from glucose into free amino acids of the brain cortex. J Neurochem 5:339–348

    Article  PubMed  CAS  Google Scholar 

  • Bergener M, Reisberg B (1989) Diagnosis and treatment of senile dementia. Springer, Berlin Heidelberg New York Tokyo

    Google Scholar 

  • Bigl V, Arendt T, Biesold D (1990) The nucleus basalis of Meynert during aging and in dementing disorders. In: Steriade M, Biesold D (eds) Cholinergic systems of the basal forebrain. Oxford University Press, Oxford

    Google Scholar 

  • Blusztajn JK, Wurtman RJ (1983) Choline and cholinergic neurons. Science 221:614–620

    Article  PubMed  CAS  Google Scholar 

  • Blusztajn JK, Maire JC, Tacconi MT, Wurtman RJ (1984) The possible role of neuronal choline metabolism in the pathophysiology of Alzheimer’s disease: a hypothesis. In: Wurtman RJ, Corkin SH, Growdon JH (eds) Alzheimer’s disease: advances in basic research and therapies. Center Brain Sci. Metab., Cambridge/Mass., pp 183–198

    Google Scholar 

  • Bowen DM, White P, Spillane JA et al. (1979) Accelerated ageing or selective neuronal loss as an important cause of dementia? Lancet I:11–14

    Google Scholar 

  • Bowen DM, Davison AN (1986) Biochemical studies of nerve cells and energy metabolism in Alzheimer’s disease. Br Med Bull 42:75–80

    PubMed  CAS  Google Scholar 

  • Cohen PJ, Alexander SC, Smith TC, Reivich M, Wollman H (1967) Effects of hypoxia and normocarbia on cerebral blood flow and metabolism in conscious man. J Appl Physiol 23:183–189

    PubMed  CAS  Google Scholar 

  • Cotman CW, Monaghan DT, Ottersen OP, Storm-Mathisen J (1987) Anatomical organization of excitatory amino acid receptors and their pathways. TINS 10:273–280

    CAS  Google Scholar 

  • Davies KJA, Goldberg AL (1987) Oxygen radicals stimulate intracellular proteolysis and lipid peroxidation by independent mechanisms in erythrocytes. J Biol Chem 262:8220–8226

    PubMed  CAS  Google Scholar 

  • Erecinska M, Silver IA (1989) ATP and brain function. J Cereb Blood Flow Metabol 9:2–19

    Article  CAS  Google Scholar 

  • Farooqui AA, Liss L, Horrocks LA (1988) Neurochemical aspects of Alzheimer’s disease: involvement of membrane phospholipids. Metabol Brain Dis 3:19–35

    Article  CAS  Google Scholar 

  • Freed WY, Michaelis EK (1976) Effect of intraventricular glutamic acid on the acquisition, performance and extinction of an operant response and on general activity. Psychopharmacology 50:293–299

    Article  PubMed  CAS  Google Scholar 

  • Freed WY, Wyatt RJ (1981) Impairment of instrumental learning in rats by glutamic acid diethyl ester. Pharmacol Biochem Behav 14:223–226

    Article  PubMed  CAS  Google Scholar 

  • Friedland RP, Jagust WJ, Huesman RH et al. (1989) Regional cerebral glucose transport and utilization in Alzheimer’s disease. Neurology 39:1427–1423

    PubMed  CAS  Google Scholar 

  • Gibbs EL, Lennox WG, Nims LF, Gibbs FA (1942) Arterial and cerebral venous blood. Arterial-venous differences in man. J Biol Chem 144:325–332

    CAS  Google Scholar 

  • Gibson GE, Jope R, Blass JP (1975) Reduced synthesis of acetylcholine accompanying impaired oxidation of pyruvic acid in rat brain minces. Biochem J 148:17–29

    PubMed  CAS  Google Scholar 

  • Goate AM, Haynes AR, Owen MJ et al. (1989) Predisposing locus for Alzheimer’s disease on chromosome 21. Lancet I:352–355

    Article  Google Scholar 

  • Gold PE, Zornetzer SF (1983) The mnemon and juices: neuromodulation of memory processes. Behav Neural Biol 38:151–189

    Article  PubMed  CAS  Google Scholar 

  • Gottstein U, Bernsmeier A, Sedlmeyer I (1963) Der Kohlenhydratstoffwechsel des menschlichen Gehirns. I. Untersuchungen mit substratspezifischen enzymatischen Methoden bei normaler Himdurehblutung. Klin Wochenschr 41:943–948

    Article  PubMed  CAS  Google Scholar 

  • Harrefeld A van, Fifkova E (1974) Involvement of glutamate in memory formation. Brain Res 81:455–467

    Article  Google Scholar 

  • Hertz MM, Paulson OB, Barry DI, Christiansen JS, Svendsen PA (1981) Insulin increases glucose transfer across the blood brain barrier. J Clin Invest 67:597–604

    Article  PubMed  CAS  Google Scholar 

  • Hoyer S (1970) Der Aminosäurenstoffwechsel des normalen menschlichen Gehirns. Klin Wochenschr 48:1239–1243

    Article  PubMed  CAS  Google Scholar 

  • Hoyer S (1982) The abnormally aged brain. Its blood flow and oxidative metabolism. A review-part II. Arch Gerontol Geriatr 1:195–207

    Article  PubMed  CAS  Google Scholar 

  • Hoyer S (1988 a) Glucose and related brain metabolism in dementia of Alzheimer type and its morphological significance. Age 11:158–166

    Article  Google Scholar 

  • Hoyer S (1988 b) Therapie zerebraler Durchblutungsstörungen. In: Trübestein G (Hrsg) Periphere und zerebrale arterielle Durchblutungsstörungen. Perimed, Erlangen, S 94–107

    Google Scholar 

  • Hoyer S, Nitsch R (1989) Cerebral excess release of neurotransmitter amino acids subsequent to reduced cerebral glucose metabolism in early-onset dementia of Alzheimer type. J Neural Transm 75:227–232

    Article  PubMed  CAS  Google Scholar 

  • Hoyer S, Nitsch R, Oesterreich K (1991) Predominant abnormality in cerebral glucose utilization in late-onset dementia of the Alzheimer type: a cross-sectional comparison against advanced late-onset and incifient early-onset cases. J Neural Transm (P-D Sect) 3:1–14

    Article  CAS  Google Scholar 

  • Hoyer S, Oesterreich K, Wagner O (1988) Glucose metabolism as the site of the primary abnormality in early-onset dementia of Alzheimer type? J Neurol 235:143–148

    Article  PubMed  CAS  Google Scholar 

  • Iwangoff P, Armbruster R, Enz A, Meier-Ruge W, Sandoz P (1980) Glycolytic enzymes from human autopic brain cortex: normally aged and demented cases. In: Roberts PJ (ed) Biochemistry of dementia. Wiley, Chichester, pp 258–262

    Google Scholar 

  • Jahr CE, Stevens CF (1987) Glutamate activates multiple single channel conductances in hippocampal neurons. Nature 325:522–525

    Article  PubMed  CAS  Google Scholar 

  • Jaspers K (1959) Allgemeine Psychopathologie, 7. Aufl. Springer, Berlin Göttingen Heidelberg, S180–187

    Google Scholar 

  • Jellinger K (1976) Neuropathological aspects of dementias resulting from abnormal blood and cerebrospinal fluid dynamics. Acta Neurol Belg 76:83–102

    PubMed  CAS  Google Scholar 

  • Johnson JW, Ascher P (1987) Glycine potentiates the NMD A response in cultured mouse brain neurons. Nature 325:529–531

    Article  PubMed  CAS  Google Scholar 

  • Khachaturian ZS (1989) The role of calcium regulation in brain aging: reexamination of a hypothesis. Aging 1:17–34

    PubMed  CAS  Google Scholar 

  • Ksiezak-Reding H, Blass JP, Gibson GE (1982) Studies on the pyruvate dehydrogenase complex in brain with the arylamine acetyltransferase-coupled assay. J Neurochem 38:1627–1636

    Article  PubMed  CAS  Google Scholar 

  • Lynch G, Baudry M (1984) The biochemistry of memory: a new and specific hypothesis. Science 224:1057–1063

    Article  PubMed  CAS  Google Scholar 

  • Mann DMA, Yates PO, Marcyniuk B (1984) Alzheimer’s presenile dementia, senile dementia of Alzheimer type and Down’s syndrome in middle age form an age related continuum of pathological changes. Neuropathol Appl Neurobiol 10:185–207

    Article  PubMed  CAS  Google Scholar 

  • McCabe BJ, Horn G (1988) Learning and memory: regional changes in N-methyl-D- aspartate receptors in the chick brain after imprinting. Proc Natl Acad Sci USA 85:2849–2853

    Article  PubMed  CAS  Google Scholar 

  • Monaghan DT, Holets VR, Toy DW, Cotman CW (1983) Anatomical distributions of four pharmacologically distinct 3H-L-glutamate binding sites. Nature 306:176–179

    Article  PubMed  CAS  Google Scholar 

  • Nagarajan S, Theodore DR, Abraham J, Balasubramanian AS (1988) Free fatty acids, lipid peroxidation, and lysosomal enzymes in experimental focal cerebral ischemia in primates: Loss of lysosomal latency by lipid peroxidation. Neurochem Res 13:193–201

    Article  PubMed  CAS  Google Scholar 

  • Novelli A, Reilly JA, Lysko PG, Henneberry RC (1988) Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced. Brain Res 451:205–212

    Article  PubMed  CAS  Google Scholar 

  • Olney JW, Ho OL, Rhee V (1971) Cytotoxic effects of acidic and sulphur containing amino acids on the infant mouse central nervous system. Exp Brain Res 14:61–76

    Article  PubMed  CAS  Google Scholar 

  • Perry EK, Perry RH, Tomlinson BE, Blessed G, Gibson PH (1980) Coenzyme A acetylating enzymes in Alzheimer’s disease: possible cholinergic „compartment“ of pyruvate dehydrogenase. Neurosci Lett 18:105–110

    Article  PubMed  CAS  Google Scholar 

  • Polinsky RJ, Noble H, DiChiro G, Nee LE, Feldman RG, Brown RT (1987) Dominantly inherited Alzheimer’s disease: cerebral glucose metabolism. J Neurol Neurosurg Psychiatry 50:752–757

    Article  PubMed  CAS  Google Scholar 

  • Procter AW, Palmer AM, Francis PT et al. (1988) Evidence of glutamatergic denervation and possible abnormal metabolism in Alzheimer’s disease. J Neurochem 50:790–802

    Article  PubMed  CAS  Google Scholar 

  • Roth M (1986) The association of clinical and neurological findings and its bearing on the classification and aetiology of Alzheimer’s disease. Br Med Bull 42:42–50

    PubMed  CAS  Google Scholar 

  • Rothman S (1984) Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death. J Neurosci 4:1884–1891

    PubMed  CAS  Google Scholar 

  • Rothman SM, Olney JW (1986) Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann Neurol 19:105–111

    Article  PubMed  CAS  Google Scholar 

  • Sacks W (1965) Cerebral metabolism of doubly labeled glucose in human in vivo. J Appl Physiol 20:117–130

    PubMed  CAS  Google Scholar 

  • Sahai S, Buselmaier W, Brussmann A (1985) 2-Amino-4-phosphobutyric acid selectively blocks two way avoidance learning. Neurosci Lett 56:137–142

    Article  PubMed  CAS  Google Scholar 

  • Sheu KFR, Kim YP, Blass JP, Weksler ME (1985) An immunochemical study of the pyruvate dehydrogenase deficit in Alzheimer’s disease brain. Ann Neurol 17:444–449

    Article  PubMed  CAS  Google Scholar 

  • Siesjö BK (1978) Brain energy metabolism, Chapt 1 and 6. Wiley, Chichester

    Google Scholar 

  • Siesjö BK (1981) Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metabol 1:155–185

    Article  Google Scholar 

  • Siesjö BK, Wieloch T (1985) Cerebral metabolism in ischemia: neurochemical basis for therapy. Br J Anaesthesiol 57:47–62

    Article  Google Scholar 

  • Sims NR, Bowen DM, Neary D, Davison AN (1983) Metabolic processes in Alzheimer’s disease: adenine nucleotide content and production of 14CO2 from (U14-C) glucose in vitro in human neocortex. J Neurochem 41:1329–1334

    Article  PubMed  CAS  Google Scholar 

  • Sims NR, Blass JP, Murphy C, Bowen DM, Neary D (1987 a) Phosphofructokinase activity in the brain in Alzheimer’s disease. Ann Neurol 21:509–510

    Article  PubMed  CAS  Google Scholar 

  • Sims NR, Finegan JM, Blass JP, Bowen DM, Neary D (1987 b) Mitochondrial function in brain tissue in primary degenerative dementia. Brain Res 436:30–38

    Article  PubMed  CAS  Google Scholar 

  • Sorbi S, Bird ED, Blass JP (1983) Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Ann Neurol 13:72–78

    Article  PubMed  CAS  Google Scholar 

  • Spencer DG, Lal H (1983) Effects of anticholinergic drugs on learning and memory. Drug Dev Res 3:489–502

    Article  CAS  Google Scholar 

  • Strange PG (1988) The structure and mechanism of neurotransmitter receptors. Implications for the structure and function of the central nervous system. Biochem J 249:309–318

    PubMed  CAS  Google Scholar 

  • Sumpter PQ, Mann DMA, Davies CA, Yates PO, Snowdon JS, Neary D (1986) An ultra- structural analysis of the effects of accumulation of neurofibrillary tangle in pyramidal neurons of the cerebral cortex in Alzheimer’s disease. Neuropathol Appl Neurobiol 12:305–319

    Article  PubMed  CAS  Google Scholar 

  • Tomlinson BE (1980) The structural and quantitative aspects of the dementias. In: Roberts PJ (ed) Biochemistry of dementia. Wiley, Chichester, pp 15–52

    Google Scholar 

  • Tomlinson BE, Blessed G, Roth M (1970) Observations on the brains of demented old people. J Neurol Sci 11:205–242

    Article  PubMed  CAS  Google Scholar 

  • Tucek S (1967) Subcellular distribution of acetyl CoA synthetase, ATP citrate lyase, citrate synthetase, choline acetyltransferase, fumarate hydratase, and lactate dehydrogenase in mammilan brain tissue. J Neurochem 14:531–545

    Article  PubMed  CAS  Google Scholar 

  • Tucek S (1978) Acetylcholine synthesis in neurons. Chapman & Hall, London

    Google Scholar 

  • Walsh T, Tilson H, de Haven D, Mailman R, Fisher A, Hanin I (1984) AF64A, a cholinergic neurotoxin, selectively depletes acetylcholine in hippocampus and cortex and produces long-term passive avoidance and radial-arm maze deficits in the rat. Brain Res 321:91–102

    Article  PubMed  CAS  Google Scholar 

  • Wan B, la Noue KF, Cheung JY, Scaduto RC jr (1989) Regulation of citric acid cycle by calcium. J Biol Chem 264:13430–13439

    PubMed  CAS  Google Scholar 

  • Wenk GL, Grey CM, Ingram DK, Spangler EL, Olton DS (1989) Retention of maze performance inversely correlates with NMDA receptor number in hippocampus and frontal neocortex in rat. Behav Neurosci 103:688–690

    Article  PubMed  CAS  Google Scholar 

  • Westerberg E, Deshpande JK, Wieloch T (1987) Regional differences in arachidonic acid release in rat hippocampal CA1 and CA3 regions during cerebral ischemia. J Cereb Blood Flow Metabol 7:189–192

    Article  CAS  Google Scholar 

  • Wong KL, Tyce GM (1983) Glucose and amino acid metabolism in rat brain during sustained hypoglycemia. Neurochem Res 8:401–415

    Article  PubMed  CAS  Google Scholar 

  • Zanotto L, Heinemann U (1983) Aspartate and glutamate induced reactions in extracellular free calcium and sodium concentration in area CA1 of #x201C;in vitro#x201D; hippocampal slices of rats. Neurosci Lett 35:79–84

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. S. Hoyer
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Universitäts-Nervenklinik, Sigmund-Freud-Str. 25, W-5300, Bonn, Deutschland

    Hans-Jürgen Möller

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Hoyer, S. (1991). Pathobiochemische Störungen im oxydativen Hirnstoffwechsel und ihre therapeutische Beeinflußbarkeit. In: Möller, HJ. (eds) Hirnleistungsstörungen im Alter. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76767-8_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-76767-8_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-54274-2

  • Online ISBN: 978-3-642-76767-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation