Summary
Although gene hunting has been carried out in Down Syndrome (DS) cells, information on expressional differences in DS brain is limited. We have recently described expressional differences in fetal DS brain but cannot assign these findings to “DS per” se or simply to “neurodegeneration”.
We therefore performed gene hunting in cerebellum of adult patients with DS and Alzheimer’s disease (AD) neuropathology, AD and controls. The gene hunting method used was differential display and pools of the individual groups were examined to rule out allelic differences.
Differential display revealed the absence of a band, identified by sequencing and gene bank work as matching the NADH3 gene (99.1% identity) in cerebellum of DS patients. Dot blots showed the presence of NADH3 signals in only two out of 7 DS patients.
We show at the transcriptional level that a mitochondrial enzyme, the complex I, NADH3, is significantly downregulated in DS cerebellum. This extends previous work on deficiencies of the electron transport chain in platelets of patients with DS.
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References
Arnason U, Xu X, Gullberg A (1996) Comparison between the complete DNA sequences of homo and the common chimpanzee based on non-chimeric sequences. J Mol Evol 42: 145–152
Benzi G, Moretti A (1995) Are reactive oxygen species involved in Alzheimer’s disease? Neurobiol Aging 16: 661–674
Burger PC, Vogel FS (1973) The development of pathologic changes of Alzheimer’s disease and senile dementia in patients with Down’s syndrome. Am J Pathol 73: 457–476
Busciglio J, Yankner BA (1995) Apoptosis and increased generation of reactive oxygen species in Down’s syndrome neurons in vitro. Nature 378: 776–779
Casserino DS, Bennett JP (1999) An evaluation of the role of mitochondria in neurodegenerative diseases: mitochondrial mutations and oxidative pathology, protective nuclear Responses and cell death in neurodegeneration. Brain Res Rev 29: 1–25
Chen H, Morris MA, Rossier C, Blouin JL, Antonarakis SE (1995) Cloning of the cDNA for the human ATP synthase OSCP subunit (ATP50) by exon trapping and mapping to chromosome 21q22.1-q22.2. Genomics 28: 470–476
De Coo RFM, Buddiger P, Smeets HJM, van Oost BA (1997) Molecular cloning and characterization of the human mitochondrial NADH:oxidoreductase 10kDa gene (NDUFV3). Genomics 45: 434–437
Epstein CJ (1992) Down Syndrome (Trisomy 21) In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. McGraw Hill, New York, pp 749–794
Gabuzda D, Busciglio J, Chen LB, Matsudiara P, Yankner B (1994) Inhibition of energy metabolism alters the processing of the amyloid precursor protein and indeuces a potentialoly amyloidogenic derivative. J Biol Chem 269: 13623–13628
Greber-Platzer S, Schatzmann-Turhani D, Wollenek G, Lubec G (1999) Evidence against the current hypothesis of “gene dosage effects” of trisomy 21: ets2, encoded on chromosome 21 is not overexpressed in hearts of patienjts with Down Syndrome. Biochem Biophys Res Commun 254: 395–399
Hardmeier R, Hoeger H, Khoshsorur A, Lubec G (1997) Transcription and activity of superoxide dismutase, catalase and glutathione peroxidase following irradiation in radiation resistant and radiation sensitive mice. Proc Natl Acad Sci USA 94: 7572–7576
Hayn M, Kremser K, Singewald N, Nemethova M, Lubec G (1996) Evidence against the involvement of active oxygen species in the pathogenesis of Down Syndrome and Alzheimer Disease. Life Sci 59: 537–544
Kitzmueller E, Labudova O, Cairns N, Lubec G (1999) Differences in gene expression in fetal Down Syndrome brain. J Neural Transm (this volume)
Labudova O, Krapfenbauer K, Moenkemann H, Rink H, Kitzmüller E, Cairns N, Lubec G (1998) Decreased transcription factor junD in brains of patients with Down Syndrome. Neurosci Lett 252: 159–162
Labudova O, Kitzmueller E, Rink H, Cairns N, Lubec G (1999) Gene expression in fetal Down Syndrome brain as revealed by subtractive hybridization. J Neural Transm (this volume)
Labudova O, Kitzmüller E, Rink H, Cairns N, Lubec G (1999) Increased phosphoglycer-ate kinase in brains of patients with Down’s syndrome but not with Alzheimer’s disease. Clin Sci 96: 279–285
Markesberry WR (1997) Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 23: 134–147
Mirra SS, Heyman A, McKeel D, Sumi S, Crain BJ (1991) The consortium to establish a registry for Alzheimer’s disease (CERAD). II. Standardization of the neuropatho-logical assessment of Alzheimer’s disease. Neurology 41: 479–486
Parker WD, Parks JK, Filley CM, Kleinschmidt-DeMasters (1994) Electron transport defects in Alzheimer’s disease braqin. Neurology 44: 1090–1096
Prince J, Jia S, Bave U, Anneren G, Oreland L (1994) Mitochondrial enzyme deficiencies in Down’s syndrome. J Neural Transm [PD-Sect] 8: 171–181
Seidl R, Schuller E, Cairns N, Lubec G (1997) Evidence against increased glycoxidation in Alzheimer’s disease. Neurosci Lett 232: 49–52
Seidl R, Greber S, Schuller E, Bernert G, Cairns N, Lubec G (1997) Evidence against increased oxidative DANN-damage in Down Syndrome. Neurosci Lett 235:137–140
Smith TS, Bennett Jr JP (1997) Mitochondrial toxins in neurodegenerative diseases. I. In vivo brain hydroxyl radical production during systemic MPTP treatment or following microdialysis infusion of methylpyridinium or azide ions. Brain Res 765: 183–186
Swerdlow RH, Parks JK, Cassarino DS, Maguire DJ, Maguire RS, Bennett Jr JP, Davis RE, Parker Jr WD (1997) Cybrids in Alzheimer’s disease: a cellular model of the disease? Neurology 49: 918–925
Tierney MC, Fisher RH, Lewis AJ, Torzitto ML, Snow WG, Reid DW, Nieuwstraten P, Van Rooijen LAA, Derks HJMG, Van Wijk R, Bischop A (1988) The NINCDA-ADRDA work group criteria for the clinical diagnosis of probable Alzheimer’s disease. Neurology 38: 359–364
Wisniewski KE, Wisniewski HM, Wen GY (1985) Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down’s syndrome. Ann Neurol 17: 278–282
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© 1999 Springer-Verlag Wien
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Krapfenbauer, K., Yoo, B.C., Cairns, N., Lubec, G. (1999). Differential display reveals deteriorated mRNA levels of NADH3 (complex I) in cerebellum of patients with Down Syndrome. In: Lubec, G. (eds) The Molecular Biology of Down Syndrome. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6380-1_13
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DOI: https://doi.org/10.1007/978-3-7091-6380-1_13
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-83377-3
Online ISBN: 978-3-7091-6380-1
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