Skip to main content
SpringerLink
Log in

Glucose-6-phosphate dehydrogenase expression associated with NADPH-dependent reactions in cerebellar neurons

  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

This review describes the variation of glucose-6-phosphate dehydrogenase (G6PD) activity in the main neurons of the molecular and granular layers as well as in the deep nuclei of the cerebellum as observed so far by optical and electron microscopy studies. Light microscopy and semiquantitative microphotometry of histochemical staining showed that the highest G6PD activity was expressed by Purkinje cells and neurons of the deep cerebellar nuclei; the elements of the molecular layer showed a diffuse G6PD staining, while the granular layer displayed only scattered G6PD activity. Electron microscopy analysis showed that the basket and stellate cells, as well as the Golgi cells, have a remarkable G6PD activity, while in the granule cells the enzyme was barely detectable. The results show that cerebellar G6PD activity changes with different neuron types as a function of its role in sustaining NADPH dependent pathways in these cells.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Greger R, Windhorst U. Comprehensive human physiology. Berlin: Springer-Verlag, 1996.

    Google Scholar 

  2. Laine J, Axelrad H. Morphology of the Golgi-impregnated Lugaro cell in the rat cerebellar cortex: a reappraisal with a description of its axon. J Comp Neurol 1996; 375: 618–640.

    Article  PubMed  CAS  Google Scholar 

  3. Guennon R, Fiddes RJ, Gouezou M, Lombes M, Baulieu EE. A key enzyme in the biosynthesis of neurosteroids, e beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta-HDS), is expressed in rat brain. Brain Res Mol Brain Res 1995; 30: 287–300.

    Article  Google Scholar 

  4. Ukena K, Usui M, Kohchi C, Tsutsui K. Cytochrome P450 sidechain cleavage enzyme in the cerebellar purkinje neuron and its neonatal change in rats. Endocrinol 1998; 139: 137–147.

    Article  CAS  Google Scholar 

  5. Moreno S, Mugnaini E, Ceru P. Immunocytochemical localization of catalase in the central nervous system of the rat. J Histochem Cytochem 1995; 43: 1253–1267.

    PubMed  CAS  Google Scholar 

  6. Lawrence GM, Beesley ACH, Mason GI, Matthews JB. Histochemical determination of Km and Vmax for hexochinase type I in three layer of rat cerebellum. Biochem SocTransact 1990; 18: 594–595.

    CAS  Google Scholar 

  7. Bronzetti E, Felici L, Ferrante F, Amenta F. Age-related changes of the metabolic profile of rat cerebellar cortex: enzyme histochemical study. Mech Ageing Dev 1988; 44: 277–286.

    Article  PubMed  CAS  Google Scholar 

  8. Bertoni-Freddari C, Fattoretti P, Casoli T, Di Stefano G, Solazzi M, Gracciotti N et al. Mapping of mitochondrial metabolic competence by cytochrome oxidase and succinic dehydrogenase cytochemistry. J Histochem Cytochem 2001; 49: 1191–1192.

    PubMed  CAS  Google Scholar 

  9. Biagiotti E, Guidi L, Capellacci S, Ambrogini P, Papa S, Del Grande P et al. Glucose-6-phosphate dehydrogenase supports the functioning of the synapses in rat cerebellar cortex. Brain Res 2001; 911: 152–157.

    Article  PubMed  CAS  Google Scholar 

  10. Philbert MA, Beiswanger CM, Roscoe TL, Waters DK, Lowndes HE. Enhanced resolution of histochemical distribution of glucose-6-phosphate dehydrogenase activity in rat neural tissue by use of a semipermeable membrane. J Histochem Cytochem 1991; 39: 937–943.

    PubMed  CAS  Google Scholar 

  11. Luzzatto L. Glucose-6-phosphate dehydrogenase deficiency and the pentose phosphate pathway. In: Handin RI, Lux SE, Stossel TP, editors. Blood: principles and practice of hematology. Philadelphia: J.B. Lippincott Company, 1995.

    Google Scholar 

  12. Pandolfi PP, Sonati F, Rivi R, Mason P, Grosveld F, Luzzatto L. Targeted disruption of the housekeeping gene encoding glucose 6-phosphate dehydrogenase (G6PD): G6PD is dispensable for pentose synthesis but essential for defense against oxidative stress. EMBO J 1995; 14: 5209–5215.

    PubMed  CAS  Google Scholar 

  13. Reiter RJ. Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J 1995; 9: 526–533.

    PubMed  CAS  Google Scholar 

  14. Romero FJ, Monsalve E, Hermenegildo C, Puertas FJ, Higueras V, Nies E et al. Oxygen toxicity in the nervous tissue: comparison of the antioxidant defense of rat brain and sciatic nerve. Neurochem Res 1991; 16: 157–161.

    Article  PubMed  CAS  Google Scholar 

  15. Baquer NZ, Hothersall JS, McLean P. Function and regulation of the pentose phosphate pathway in brain. In: Horeker B, Stadtman ER., editors. Current Topics in Cellular Regulation. New York: Academic Press, 1988: 265–289.

    Google Scholar 

  16. Ninfali P, Biagiotti E, Guidi L, Malatesta M, Gazzanelli G, Del Grande P. Cytochemical and immunocytochemical methods for electron microscopic detection of glucose-6-phosphate dehydrogenase in brain areas. Brain Res Prot 2000; 5: 115–120.

    Article  CAS  Google Scholar 

  17. Van Noorden CJ, Frederiks WM. Enzyme Histochemistry: a laboratory manual of current methods. New York: Oxford University Press, 1992.

    Google Scholar 

  18. Ninfali P, Aluigi G, Balduini W, Pompella A. Glucose-6-phosphate dehydrogenase activity is higher in the olfactory bulb than in other brain areas. Brain Res 1997; 744: 138–142.

    Article  PubMed  CAS  Google Scholar 

  19. Biagiotti E, Bosch KS, Ninfali P, Frederiks WM, Van Noorden CJ. Posttranslational regulation of glucose-6-phosphate dehydrogenase activity in tongue epithelium. J Histochem Cytochem 2000; 48: 971–977.

    PubMed  CAS  Google Scholar 

  20. Butcher RG. The measurement in tissue sections of the two formazans derived from nitroblue tetrazolium in dehydrogenase reactions. Histochem J 1978; 10: 739–744.

    Article  PubMed  CAS  Google Scholar 

  21. Berchtold JP. Ultrastructural demonstration of glucose-6-phosphate dehydrogenase activity in steroid-secreting cells. Histochemistry 1979; 63: 173–180.

    Article  PubMed  CAS  Google Scholar 

  22. Hajos F, Kerpel-Fronius S. Electron histochemical observation of succinic dehydrogenase activity in various parts of neurones. Exp Brain Res 1969; 8: 66–78.

    Article  PubMed  CAS  Google Scholar 

  23. Sakharova AV, Salimova NB, Sakharov DA. Peculiar cells notable for very high activity of glucose-6-phosphate dehydrogenase in the mammalian medulla oblongata. A histochemical and electron microscopic study. Neuroscience 1979; 4: 1173–1177.

    Article  PubMed  CAS  Google Scholar 

  24. Biagiotti E, Malatesta M, Capellacci S, Fattoretti P, Gazzanelli G, Ninfali P. Quantification of G6PD in small and large intestine of rat during aging. Acta Histochem 2002; 104: 225–234.

    Article  PubMed  CAS  Google Scholar 

  25. Contestabile A, Andersen H. Methodological aspects of the histochemical localization and activity of some cerebellar dehydrogenases. Histochemistry 1978; 56: 117–132.

    Article  PubMed  CAS  Google Scholar 

  26. Ninfali P, Guidi L, Aluigi G, Biagiotti E, Del Grande P. High glucose-6-phosphate dehydrogenase activity contributes to the structural plasticity of periglomerular cells in the olfactory bulb of adult rats. Brain Res 1999; 819: 150–154.

    Article  PubMed  CAS  Google Scholar 

  27. Wells PG, Kim PM, Laposa RR, Nicol CJ, Parman T, Winn LM. Oxidative damage in chemical teratogenesis. Mutation Res 1997; 396: 65–78.

    PubMed  CAS  Google Scholar 

  28. Dìez-Fernàndez C, Sanz N, Cascales M. Changes in glucose-6-phosphate dehydrogenase and malic enzyme gene expression in acute hepatic injury induced by thioacetamide. Biochem Pharmacol 1996; 51: 1159–1163.

    Article  PubMed  Google Scholar 

  29. Salvemini F, Franzé A, Iervolino A, Filosa S, Salzano S, Ursini MV. Enhanced glutathione levels and oxidoresistence mediated by increased glucose-6-phosphate dehydrogenase expression. J Biol Chem 1999; 274: 2750–2757.

    Article  PubMed  CAS  Google Scholar 

  30. Ursini MV, Parrella A, Rosa G, Salzano S, Martini G. Enhanced expression of glucose-6-phosphate dehydrogenase in human cells sustaining oxidative stress. Biochem J 1997; 323: 801–806.

    PubMed  CAS  Google Scholar 

  31. Tsutsui K, Ukena K. Neurosteroids in the cerebellar Purkinje neuron and their actions. Int J Mol Med 1999; 4: 49–56.

    PubMed  CAS  Google Scholar 

  32. Baulieu EE. Neurosteroids: a novel function of the brain. Psychoneuroendocrinol 1998; 23: 963–987.

    Article  CAS  Google Scholar 

  33. Compagnone NA, Mellon SH. Neurosteroids: biosynthesis and function of these novel neuromodulators. Front Neuroendocrinol 2000; 21: 1–56.

    Article  PubMed  CAS  Google Scholar 

  34. Mellon SH, Vaudry H. Biosynthesis of neurosteroids and regulation of their synthesis. In: Biggio G, Purdy RH, editors. Neurosteroids and Brain Function. San Diego: Academic Press, 2001: 34–78.

    Google Scholar 

  35. Philbert MA, Beiswanger CM, Waters DK, Reuhl KR, Lowndes HE. Cellular and regional distribution of reduced glutathione in the nervous system of the rat: histochemical localization by mercury orange and o-phthaldialdehyde-induced histofluorescence. Toxicol Appl Pharmacol 1991; 107: 215–227.

    Article  PubMed  CAS  Google Scholar 

  36. Fonnum F, Lock EA. Cerebellum as a target for toxic substances. Toxicol Lett 2000; 112: 9–16.

    Article  PubMed  Google Scholar 

  37. Kudo H, Kokunai T, Kondoh T, Tamaki N, Matsumoto S. Quantitative analysis of glutathione in rat central nervous system: comparison of GSH in infant brain with that in adult brain. Brain Res 1990; 511: 326–328.

    Article  PubMed  CAS  Google Scholar 

  38. Kirstein CL, Coopersmith R, Bridges RJ, Leon M. Glutathione levels in olfactory and non-olfactory neural structures of rats. Brain Res 1991; 543: 341–346.

    Article  PubMed  CAS  Google Scholar 

  39. Bredt DS, Hwang PM, Snyder SH. Localization of nitric oxide syntase indicating a neural role for nitric oxide. Nature 1990; 347: 768–770.

    Article  PubMed  CAS  Google Scholar 

  40. Baader S, Schilling K. Glutamate receptors mediate dynamic regulation of nitric oxide synthase expression in cerebellar granule cells. J Neurosci 1996; 16: 1440–1449.

    PubMed  CAS  Google Scholar 

  41. Wood PL, Emmet MR, Wood JA. Involvement of granule, basket and stellate neurons but not Purkinje or Golgi cells in cerebellar cGMP increases in vivo. Life Sci 1994; 54: 615–620.

    Article  PubMed  CAS  Google Scholar 

  42. Nathan C, Xie Q. Nitric oxide synthases: roles, tolls, and controls. Cell 1994; 78: 915–918.

    Article  PubMed  CAS  Google Scholar 

  43. Takeuchi Y, Kimura H, Sano Y. Immunohistochemical demonstration of serotonin-containing nerve fibers in the cerebellum. Cell Tissue Res 1982; 226: 1–12.

    PubMed  CAS  Google Scholar 

  44. Bishop GA, Ho RH. The distribution and origin of serotonin immunoreactivity in the rat cerebellum. Brain Res 1985; 331: 195–207.

    Article  PubMed  CAS  Google Scholar 

  45. Thöny B, Auerbach G, Blau N. Tetrahydrobiopterin biosynthesis, regeneration and functions. Biochem J 2000; 347: 1–16.

    Article  PubMed  Google Scholar 

  46. Kletzien RF, Harris PK, Foellmi LA. Glucose-6-phosphate dehydrogenase: a “housekeeping” enzyme subject to tissue-specific regulation by hormones, nutrients, and oxidant stress. FASEB J 1994; 8: 174–181.

    PubMed  CAS  Google Scholar 

  47. Franzé A, Ferrante MI, Fusco F, Santoro A, Sanzari E, Martini G et al. Molecular anatomy of the human glucose-6-phosphate dehydrogenase core promoter. FEBS letters 1998; 437: 313–318.

    Article  PubMed  Google Scholar 

  48. Mehlen P, Kretz-Remy C, Prèville X, Arrigo AP. Human hsp27 Drosophila hsp27 and human αB-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNFα-induced cell death. EMBO J 1996; 15: 2695–2706.

    PubMed  CAS  Google Scholar 

  49. Kane DJ, Sarafian TA, Anton R, Hahn H, Gralla EB, Valentine JS et al. Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species. Science 1993; 262(5137): 1274–1277.

    Article  PubMed  CAS  Google Scholar 

  50. Kirkman HN, Rolfo M, Ferraris AM, Gaetani GF. Mechanism of protection of catalase by NADPH. J Biol Chem 1999; 20: 13908–13914.

    Article  Google Scholar 

  51. Yen DT, Luo CB, Shen WZ, Chow PH, Zheng DR, Yu MC. Tyrosine hydroxylase and dopamine-ß-hydoxylase positive neurons and fibers in the developing human cerebellum an immunohistochemical study. Neuroscience 1995; 65: 453–461.

    Article  Google Scholar 

  52. Ninfali P, Biagiotti E. Glucose-6-phosphate dehydrogenase and the hexose monophosphate shunt in the nervous system. Recent research development in neurochemistry 2003: 263–283.

  53. Mattson MP, Goodman Y. Different amyloidogenic peptides share a similar mechanism of neurotoxicity involving reactive oxygen species and calcium. Brain Res 1995; 676: 219–224.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Biochemistry “G. Fornaini”, University of Urbino, Urbino, Italy

    Enrica Biagiotti & Paolino Ninfali (Prof.)

  2. Institute of Morphology, Sogesta, University of Urbino, Urbino, Italy

    Loretta Guidi & Paolo Del Grande

Authors
  1. Enrica Biagiotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Loretta Guidi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paolo Del Grande
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paolino Ninfali
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paolino Ninfali.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Biagiotti, E., Guidi, L., Del Grande, P. et al. Glucose-6-phosphate dehydrogenase expression associated with NADPH-dependent reactions in cerebellar neurons. Cerebellum 2, 178–183 (2003). https://doi.org/10.1080/14734220310016123

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/14734220310016123

Keywords

Search

Navigation