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c-fos expression in brains of patients with Down Syndrome

  • S. Greber-Platzer
  • B. Balcz
  • N. Cairns
  • G. Lubec
Conference paper

Summary

c-fos is a protooncogene serving in multiple physiological processes in brain from signalling to proliferation and synaptic plasticity. We therefore decided to determine this transcription factor in control and Down Syndrome (DS) brain with the Rationale that c-fos may be linked to brain damage in DS.

We determined mRNA steady state levels in frontal, parietal, occipital, temporal cortex and cerebellum of 9 patients with DS and 9 controls using RT-PCT.

Significantly increased levels of mRNA c-fos normalized versus the housekeeping gene beta-actin mRNA were found in frontal, parietal and temporal cortex of DS brain. c-fox mRNA levels comparable to controls were found in occipital cortex and cerebellum.

Deteriorated c-fos expression in the individual brain regions may be linked to increased apoptosis and neurodegeneration, overexcitation by excitatory amino acids or reactive oxygen species.

Keywords

Quisqualic Acid Individual Brain Region Synaptic NMDA Receptor Activation Cfos mRNA 
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.

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References

  1. Chomczynski P, Sacchi N (1987) Single — step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159PubMedCrossRefGoogle Scholar
  2. Cole AJ, Saffen DW, Baraban JM, Worley PF (1989) Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation. Nature 340: 474–476PubMedCrossRefGoogle Scholar
  3. Contestabile A, Ciani E, Sparapani M, Guarnieri T, Dell’Erba G, Bologna F, Cicognani C (1998) Activation of the Ornithin decarboxylase-polyamine system and induction of c-fos and p53 expression in relation to excitotoxic neuronal apoptosis in normal and microencephalic rats. Exp Brain Res 120: 519–526PubMedCrossRefGoogle Scholar
  4. Dragunow M Abraham WC, Goulding M, Mason SE, Robertson HA, Faull RL (1989) Long-term potentiation and the induction of c-fos mRNA and proteins in the dentate gyrus of unanaesthetized rats. Neurosci Lett 101: 274–280PubMedCrossRefGoogle Scholar
  5. Figiel I, Kacmarek L (1997) Cellular and molecular correlates of glutamate-evoked neuronal programmed cell death in the in vitro cultures of rat hippocampal dentate gyrus. Neurochem Int 31: 229–240PubMedCrossRefGoogle Scholar
  6. Gillardon F, Skutella T, Uhlmann E, Holsboer F, Zimmermannn M, Behl C (1996) Activation of c-fos contributes to amyloid beta-peptide — induced neurotoxicity. Brain Res 706: 169–172PubMedCrossRefGoogle Scholar
  7. Giovanelli L, Casamenti F, Pepeu G (1998) C-fos expression in the rat nucleus basalis upon excitotoxic lesion with quisqualic acid: a study in adult and aged animals. J Neural Transm 105: 935–948CrossRefGoogle Scholar
  8. Hasegawa K, Litt L, Espanol MT, Sharp FR, Chan PH (1998) Expression of c-fos and hsp70 mRNA in neonatal rat cerebrocortical slices during NMDA-induced necrosis and apoptosis. Brain Res 785: 262–278PubMedCrossRefGoogle Scholar
  9. Hayn M, Kremser K, Singewald N, Cairns N, Nemethova M, Lubec B, Lubec G (1996) Evidence against the involvement of reactive oxygen species in the pathogenesis of neuronal death in Down’s syndrome and Alzheimer’s disease. Life Sci 59: 537–544PubMedCrossRefGoogle Scholar
  10. Herrera DG, Robertson HA (1996) Activation of c-fos in the brain. Progr Neurobiol 50: 83–107CrossRefGoogle Scholar
  11. Jefferey KJ, Abraham WC, Dragunow M, Mason SE (1990) Induction of Fos-like immunoreactivity and the maintenance of long-term potentiation in the dentate gyrus of unanaesthetized rats. Brain Res Mol Brain Res 8: 267–274CrossRefGoogle Scholar
  12. Lanahan A, Lyford G, Stevenson GS, Worley PF, Barnes CA (1997) Selective alteration of long term potentiation-induced transcripütional response in hippocampus of aged, memory — impaired rats. J Neurosci 17: 2876–2885PubMedGoogle Scholar
  13. MacGibbon GA, Lawlor PA, Walton M, Sirimanne E, Faull RL, Synek B, Mee E, Connor B, Dragunow M (1997) Expression of Fos, Jun, and Krox family proteins in Alzheimer’s disease. Exp Neurol 147: 316–332PubMedCrossRefGoogle Scholar
  14. Marcus DL, Strafaci JA, Miller DC, Masia S, Thomas CG, Rosman J, Hussain S, Freedman ML (1998) Quantitative neuronal c-fos and c-jun expression in Alzheimer’s disease. Neurobiol Aging 19: 393–400PubMedCrossRefGoogle Scholar
  15. Richter-Landsberg C, Vollgraf U (1998) Mode of cell injury and death after hydrogen peroxide exposure in cultured Oligodendroglia cells. Exp Cell Res 244: 218–219PubMedCrossRefGoogle Scholar
  16. Risser D, Lubec G, Cairns N, Herrera-Marschitz M (1997) Excitatory amino acids and monoamines in parahippocampal gyrus and frontal cortical pole of adults with Down syndrome. Life Sci 60: 1231–1237PubMedCrossRefGoogle Scholar
  17. Roberts LA, Higgins MJ, O’Shaugnessy CT, Stone TW, Morris BJ (1996) Changes in hippocampal gene expression associated with the induction of long-term potentiation. Brain Res-Mol Brain Res 42: 123–127PubMedCrossRefGoogle Scholar
  18. Ryabinin AE (1998) Role of hippocampus in alcohol-induced memory impairment: implications from behavioral and immediate early gene studies. Psychopharmacology 139: 34–43PubMedCrossRefGoogle Scholar
  19. Schreiber SS, Najm I, Tocco G, Baudry M (1993) Co-expression of HSP72 and c-fos in rat brain following kainic acid treatment. Neuroreport 5: 269–272PubMedCrossRefGoogle Scholar
  20. Seidl R, Greber S, Schuller E, Bernert G, Cairns N, Lubec G (1997) Evidence against increased oxidative DNA-damage in Down Syndrome. Neurosci Lett 235: 137–140PubMedCrossRefGoogle Scholar
  21. Smeyne RJ, Vendrell M, Hayward M, Baker SJ, Miao GG, Schilling K, Robertson LM, Curran T, Morgan JI (1993) Continuous c-fos expression precedes programmed cell death in vivo. Nature 363: 166–169PubMedCrossRefGoogle Scholar
  22. Walton M, MacGibbon G, Young D, Sirimanne E, Williams C, Gluckmann P, Dragunow M (1998) Do c-jun, c-Fos and amyloid precursor protein play a role in neuronal death or survival? J Neurosci Res 53: 330–342PubMedCrossRefGoogle Scholar
  23. Worley PF, Bhat RV, Baraban JM, Erickson CA, McNaughton BL, Barnes CA (1993) Thresholds for synaptic activation of transcription factors in hippocampus: correlation with long-term enhancement. J Neurosci 13: 4776–4786PubMedGoogle Scholar
  24. Yee WM, Frim DM, Isacson O (1993) Relationship between stress protein induction and NMDA-mediated neuronal death in the entorhinal cortex. Exp Brain Res 94: 193–202PubMedCrossRefGoogle Scholar
  25. Zhang P, Hirsch EC, Damier P, Duyckaerts C, Javoy-Agid F (1992) c-fos protein-like immunoreactivity: distribution in the human brain and over-expression in the hippocampus of patients with Alzheimer’s disease. Neuroscience 46: 9–21PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1999

Authors and Affiliations

  • S. Greber-Platzer
    • 1
  • B. Balcz
    • 1
  • N. Cairns
    • 2
  • G. Lubec
    • 1
  1. 1.Department of PediatricsUniversity of ViennaViennaAustria
  2. 2.Department of Neuropathology, Institute of PsychiatryUniversity of LondonUK

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