Aging-related increase in oxidative stress correlates with developmental pattern of beta-secretase activity and beta-amyloid plaque formation in transgenic Tg2576 mice with Alzheimer-like pathology
Jenny Apelt
Department of Neurochemistry, University of Leipzig, Paul Flechsig Institute for Brain Research, Jahnallee 59, D-04109 Leipzig, Germany
Search for more papers by this authorMarina Bigl
Institute for Biochemistry, University of Leipzig, Liebigstraße 16, D-04103 Leipzig, Germany
Search for more papers by this authorPatrick Wunderlich
Department of Neurochemistry, University of Leipzig, Paul Flechsig Institute for Brain Research, Jahnallee 59, D-04109 Leipzig, Germany
Search for more papers by this authorCorresponding Author
Reinhard Schliebs
Department of Neurochemistry, University of Leipzig, Paul Flechsig Institute for Brain Research, Jahnallee 59, D-04109 Leipzig, Germany
*Corresponding author. Tel.: +49 341 97 25734; fax: +49 341 97 25749.
E-mail address:[email protected] (R. Schliebs)
Search for more papers by this authorJenny Apelt
Department of Neurochemistry, University of Leipzig, Paul Flechsig Institute for Brain Research, Jahnallee 59, D-04109 Leipzig, Germany
Search for more papers by this authorMarina Bigl
Institute for Biochemistry, University of Leipzig, Liebigstraße 16, D-04103 Leipzig, Germany
Search for more papers by this authorPatrick Wunderlich
Department of Neurochemistry, University of Leipzig, Paul Flechsig Institute for Brain Research, Jahnallee 59, D-04109 Leipzig, Germany
Search for more papers by this authorCorresponding Author
Reinhard Schliebs
Department of Neurochemistry, University of Leipzig, Paul Flechsig Institute for Brain Research, Jahnallee 59, D-04109 Leipzig, Germany
*Corresponding author. Tel.: +49 341 97 25734; fax: +49 341 97 25749.
E-mail address:[email protected] (R. Schliebs)
Search for more papers by this authorAbstract
The molecular mechanisms of β-amyloidogenesis in sporadic Alzheimer's disease are still poorly understood. To reveal whether aging-associated increases in brain oxidative stress and inflammation may trigger onset or progression of β-amyloid deposition, a transgenic mouse (Tg2576) that express the Swedish double mutation of human amyloid precursor protein (APP) was used as animal model to study the developmental pattern of markers of oxidative stress and APP processing. In Tg2576 mouse brain, cortical levels of soluble β-amyloid (1–40) and (1–42) steadily increased with age, but significant deposition of fibrillary β-amyloid in cortical areas did not occur before postnatal age of 10 months. The slope of increase in cerebral cortical β-secretase (BACE1) activities in Tg2576 mice between ages of 9 and 13 months was significantly higher as compared to that of the α-secretase, while the expression level of BACE1 protein and mRNA did not change with age. The activities of superoxide dismutase and glutathione peroxidase in cortical tissue from Tg2576 mice steadily increased from postnatal age 9–12 months. The levels of cortical nitric oxide, and reactive nitrogen species demonstrated peak values around 9 months of age, while the level of interleukin-1β steadily increased from postnatal month 13 onwards. The developmental temporal coincidence of increased levels of reactive nitrogen species and antioxidative enzymes with the onset of β-amyloid plaque deposition provides further evidence that developmentally and aging-induced alterations in brain oxidative status exhibit a major factor in triggering enhanced production and deposition of β-amyloid, and potentially predispose to Alzheimer's disease.
References
- H. Akiyama, S. Barger, S. Barnum, B. Bradt, J. Bauer, G.M. Cole, N.R. Cooper, P. Eikelenboom, M. Emmerling, B.L. Fiebich, C.E. Finch, S. Frautschy, W.S. Griffin, H. Hampel, M. Hull, G. Landreth, L. Lue, R. Mrak, I.R. Mackenzie, P.L. McGeer, M.K. O'Banion, J. Pachter, G. Pasinetti, C. Plata-Salaman, J. Rogers, R. Rydel, Y. Shen, W. Streit, R. Strohmeyer, I. Tooyoma, F.L. Van Muiswinkel, R. Veerhuis, D. Walker, S. Webster, B. Wegrzyniak, G. Wenk, T. Wyss-Coray. Inflammation and Alzheimer's disease. Neurobiol. Aging 2000; 21
- M.Y. Aksenov, M.V. Aksenova, W.R. Markesbery, D.A. Butterfield. Amyloid β-peptide (1–40)-mediated oxidative stress in cultured hippocampal neurons. Protein carbonyl formation, BB expression, and the level of Cu,Zn, and Mn SOD mRNA. J. Mol. Neurosci. 10: 1998; 181–192
- A.C. Andorn, R.N. Kalaria. Factors affecting pro- and anti-oxidant properties of fragments of the b-protein precursor (bPP): implications for Alzheimer's disease. J. Alzheimer's Dis. 2: 2000; 69–78
- G. Anneren, A. Gardner, T. Lundin. Increased gluathione peroxidase activity in erythrocytes in patients with Alzheimer's disease/senile dementia of Alzheimer's type. Acta Neurol. Scand. 73: 1986; 586–589
- J. Apelt, R. Schliebs. β-Amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology. Brain Res. 894: 2001; 21–30
- M. Barkats, S. Millecamps, P. Abrioux, M.C. Geoffroy, J. Mallet. Overexpression of glutathione peroxidase increases the resistance of neuronal cells to Aβ-mediated neurotoxicity. J. Neurochem. 75: 2000; 1438–1446
- T.A. Bayer, S. Schäfer, A. Simons, A. Kemmling, T. Kamer, R. Tepest, A. Eckert, K. Schüssel, O. Eikenberg, C. Sturchler-Pierrat, D. Abramowski, M. Staufenbiel, G. Multhaup. Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Aβ production in APP23 transgenic mice. Proc. Natl. Acad. Sci. USA. 100: 2003; 14187–14192
- C. Behl. Alzheimer's disease and oxidative stress: implications for novel therapeutic approaches. Prog. Neurobiol. 57: 1999; 301–323
- I. Blasko, R. Beer, M. Bigl, J. Apelt, G. Franz, D. Rudzki, G. Ransmayr, A. Kampfl, R. Schliebs. Experimental traumatic brain injury in rat stimulates the expression, production and activity of Alzheimer's disease β-secretase (BACE-1). J. Neural Transm. 111: 2004; 523–536
- U. Bodendorf, S. Danner, F. Fischer, M. Stefani, C. Sturchler-Pierrat, K.H. Wiederhold, M. Staufenbiel, P. Paganetti. Expression of human β-secretase in the mouse brain increases the steady-state level of β-amyloid. J. Neurochem. 80: 2002; 799–806
- R.D. Brinton. A women's health issue: Alzheimer's disease and strategies for maintaining cognitive health. Int. J. Fertil. Womens Med. 44: 1999; 174–185
- Carney, J.M., Starke-Reed, P.E., Oliver, C.N., Landum, R.W., Cheng, M.S., Wu, J.F., Floyd, R.A., 1991. Reversal of age-relatedincrease in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone. In: Proceedings of the National Academy of Science, USA, 1991, vol. 88, pp. 3633–3636
- M.C. Carrillo, S. Kanai, Y. Sato, M. Nokubo, G.O. Ivy, K. Kitani. The optimal dosage of (−) deprenyl for increasing superoxide dismutase activities inseveral brainregion s decreases with age in male Fischer 344 rats. Life Sci. 52: 1993; 1925–1934
- F. Celsi, A. Ferri, A. Casciati, N. Dámbrosi, G. Rotilio, A. Costa, C. Volonté, M.T. Carri. Overexpression of superoxide dismutase 1 protects against β-amyloid peptide toxicity: effect of estrogen and copper chelators. Neurochem. Int. 44: 2004; 25–33
- H.C. Dhan, M.S. Benedetti, P. Dostert. Differential changes in superoxide dismutase activity in brain and liver of old rats and mice. J. Neurochem. 40: 1983; 1003–1007
- G. Evin, A. Zhu, R.M.D. Holsinger, C.L. Masters, Q.-X. Li. Proteolytic processing of the Alzheimer's disease amyloid precursor protein in brain and platelets. J. Neurosci. Res. 74: 2003; 386–392
- A.L. Friedlich, L.L. Butcher. Involvement of free oxygen radicals in β-amyloidosis: a hypothesis. Neurobiol. Aging. 1: 1994; 443–455
- H. Fukomoto, B.S. Cheung, B.T. Hyman, M.C. Irizarry. Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease. Arch. Neurol. 59: 2002; 1381–1389
- H. Fukomoto, D.L. Rosene, M.B. Moss, S. Raju, B.T. Hyman, M.C. Irizarry. β-Secretase activity increases with aging in human, monkey, and mouse brain. Am. J. Pathol. 164: 2004; 719–725
- E. Gahtan, J.B. Overmier. Inflammatory pathogenesis in Alzheimer's disease: biological mechanisms and cognitive sequeli. Neurosci. Behav. Rev. 23: 1999; 615–633
- E. Geremia, D. Baratta, S. Zafarana, R. Giordano, M.R. Pinizzotto, M.G. Laxx, A. Garazzo. Antioxidant enzymatic systems in neuronal and glial cell-enriched fractions of rat brain during aging. Neurochem. Res. 15: 1990; 719–723
- Y. Goodman, M.P. Mattson. Secreted forms of β-amyloid precursor protein protect hippocampal neurons against amyloid beta-peptide-induced oxidative injury. Exp. Neurol. 128: 1994; 1–12
- B. Halliwell. Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs Aging. 18: 2001; 685–716
- C. Harris-Cerruti, A. Kamsler, B. Kaplan, B. Lamb, M. Segal, Y. Groner. Functional and morphological alterations in compound transgenic mice overexpressing Cu/Zn superoxide dismutase and amyloid precursor protein. Eur. J. Neurosci. 19: 2004; 1174–1190
- M. Hartlage-Rübsamen, J. Apelt, R. Schliebs. Fibrillary beta-amyloid deposits are closely associated with atrophic nitric oxide synthase (NOS)-expressing neurons but do not upregulate the inducible NOS in transgenic Tg2576 mouse brain with Alzheimer pathology. Neurosci. Lett. 302: 2001; 73–76
- R.M. Holsinger, C.A. McLean, K. Beyreuther, C.L. Masters, G. Evin. Increased expression of the amyloid precursor β-secretase in Alzheimer's disease. Ann. Neurol. 51: 2002; 783–786
- K.K. Hsiao, D.R. Borchelt, K. Olson, R. Johannsdottir, C. Kitt, W. Yunis, S. Xu, C. Eckman, S. Younkin, D. Price, C. Iadecola, H.B. Clark, G. Carlson. Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor protein. Neuron. 15: 1995; 1203–1218
- K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, G. Cole. Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science. 274: 1996; 99–102
- S. Hussain, W. SlikkerJr., S.F. Ali. Age-related changes in antioxidant enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione in different regions of mouse brain. Int. J. Dev. Neurosci. 13: 1995; 811–817
- C. Iadecola, F. Zhang, K. Niwa, C. Eckman, S.K. Turner, E. Fischer, S. Younkin, D.R. Borchelt, K.K. Hsiao, G.A. Carlson. SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein. Nat. Neurosci. 2: 1999; 157–161
- W. Kalback, M.D. Watson, T.A. Kokjohn, Y.M. Kuo, N. Weiss, D.C. Luehrs, J. Lopez, D. Brune, S.S. Sisodia, M. Staufenbiehl, M. Emmerling, A.E. Roher. APP transgenic mice Tg2576 accumulate Aβ peptides that are distinct from the chemically modified and insoluble peptides deposited in Alzheimer's disease senile plaques. Biochemistry. 41: 2002; 922–928
- T. Kawarabayashi, L.H. Younkin, T.C. Saido, M. Shoji, K.H. Ashe, S.G. Younkin. Age-dependent changes in brain, CSF, and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer's disease. J. Neurosci. 21: 2001; 372–381
- J.N. Keller, M.S. Kindy, F.W. Holtsberg, D.K. St. Clair, H.C. Yen, A. Germeyer, S.M. Steiner, A.J. Bruce-Keller, J.B. Hutchins, M.P. Mattson. Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction. J. Neurosci. 18: 1998; 687–697
- J.Y. Khan, S.M. Black. Developmental changes in murine brain antioxidant enzymes. Pediatr. Res. 54: 2003; 77–82
- K.S. Kim, S.Y. Choi, H.Y. Kwon, M.H. Won, T.-C. Kang, J.H. Kang. Aggregation of a.synuclein induced by the Cu,Zn-superoxide dismutase and hydrogen peroxide system. Free Radic. Biol. Med. 32: 2002; 544–550
- H.-C. Kim, K. Yamada, A. Nitta, A. Olariu, M.H. Tran, M. Mizuno, A. Nakajima, T. Nagai, H. Kamei, W.-K. Jhoo, D.-H. Im, E.-J. Shin, O.P. Hjelle, O.P. Ottersen, S.C. Park, K. Kato, M.-E. Mirault, T. Nabeshima. Immunocytochemical evidence that amyloid β (1–42) impairs endogenous antioxidant systems in vivo. Neuroscience. 119: 2003; 399–419
- A. Kontush. Amyloid-beta, an antioxidant that becomes a pro-oxidant and critically contributes to Alzheimer's disease. Free Radic. Biol. Med. 31: 2001; 1120–1131
- L.A. Kotilinek, B. Bacskai, M. Westerman, T. Kawarabashi, S.G. Younkin, B.T. Hyman, S. Younkin, K.H. Ashe. Reversible memory loss in a mouse transgenic model of Alzheimer's disease. J. Neurosci. 22: 2002; 6331–6335
- M. Ledig, R. Fried, M. Ziessel, P. Mandel. Regional distribution of superoxide dismutase in rat brain during postnatal development. Brain Res. 256: 1982; 333–337
- G.P. Lim, F. Yang, T. Chu, E. Gahtan, O. Ubeda, W. Beech, J.B. Overmier, K. Hsiao-Ashe, S.A. Frautschy, G.M. Cole. Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice. Neurobiol. Aging. 22: 2001; 983–991
- M.A. Lovell, W.D. Ehmann, M.P. Mattson, W.R. Markesbery. Elevated 4-hydroxynonenal in ventricular fluid in Alzheimer's disease. Neurobiol. Aging. 18: 1997; 457–461
- O.H. Lowry, N.J. Rosebrough, A.L. Farr, R.J. Randall. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193: 1951; 265–275
- W.J. Lukiw. Gene expression profiling in fetal, aged, and Alzheimer hippocampus: a continuum of stress-related signaling. Neurochem. Res. 29: 2004; 1287–1297
- W.R. Markesbery. Oxidative stress hypothesis in Alzheimer's disease. Free Radic. Biol. Med. 23: 1997; 134–147
- L. Marlow, M. Cain, M.A. Papolla, K. Sambamurti. β-Secretase processing of the Alzheimer's amyloid protein precursor (APP). J. Mol. Neurosci. 20: 2003; 233–240
- E.G. McGeer, P.L. McGeer. Inflammatory processes in Alzheimer's disease. Prog. Neuropsychopharmacol. Biol. Psychiatry. 27: 2003; 741–749
- P. Mecocci, U. MacGarvey, M.F. Beal. Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease. Ann. Neurol. 36: 1994; 747–751
- M.A. Papolla, Y.-J. Chyan, K. Hsiao, G. Perry, M.A. Smith, P. Bozner. Evidence of oxidative stress and in vivo neurotoxicity of β-amyloid in a transgenic mouse model of Alzheimer's disease: a chronic oxidative paradigm for testing antioxidant therapies in vivo. Am. J. Pathol. 152: 1998; 871–877
- L.A. Ridnour, J.E. Sim, M.A. Hayward, D.A. Wink, S.M. Martin, G.R. Buettner, D.R. Spitz. A spectrophotometric method for the direct detection and quantitation of nitric oxide, nitrite, and nitrate in cell culture media. Anal. Biochem. 281: 2000; 223–229
- A. Rocchi, S. Pellegrini, G. Siciliano, L. Murri. Causative and susceptibility genes for Alzheimer's disease: a review. Brain Res. Bull. 61: 2003; 1–24
- S. Rossner, J. Apelt, R. Schliebs, J.R. Perez-Polo, V. Bigl. Neuronal and glial β-secretase (BACE) protein expression in transgenic Tg2576 mice with amyloid plaque pathology. J. Neurosci. Res. 64: 2001; 437–446
- P. Schubert, T. Morino, H. Miyazaki, T. Ogata, Y. Nakamura, C. Marchini, S. Ferroni. Cascading glia reactions: a common pathomechanism and its differentiated control by cyclic nucleotides signaling. Ann. NY Acad. Sci. 903: 2000; 224–233
- D.J. Selkoe. Aging, amyloid, and Alzheimer's disease: a perspective in honour of Carl Cotman. Neurochem. Res. 28: 2003; 1705–1713
- A.J. Sinclair, A.J. Bayer, J. Johnston, C. Warner, S.R. Maxweel. Altered plasma antioxidant status in subjects with Alzheimer's disease and vascular dementia. Int. J. Geriatr. Psychiatry. 13(120): 1998; 840–845
10.1002/(SICI)1099-1166(1998120)13:12<840::AID-GPS877>3.0.CO;2-R Google Scholar
- G.W. Small. The pathogenesis of Alzheimer's disease. J. Clin. Psychiatry. 59(Suppl. 9): 1998; 7–14
- M.A. Smith, P.L. Richey-Harris, L.M. Sayre, J.S. Beckman, G. Perry. Widespread peroxynitrite-mediated damage in Alzheimer's disease. J. Neurosci. 17: 1997; 2653–2657
- M.A. Smith, K. Hirai, K. Hsiao, M.A. Papolla, P.L.R. Harris, S.L. Siedlak, M. Tabaton, G. Perry. Amyloid-β deposition in Alzheimer transgenic mice is associated with oxidative stress. J. Neurochem. 70: 1998; 2212–2215
- G.L. Wenk, K. McGann-Gramling, B. Hauss-Wegrzyniak, D. Ronchetti, R. Maucci, S. Rosi, L. Gasparini, E. Ongini. Attenuation of chronic neuroinflammation by a nitric oxide-releasing derivative of the antioxidant ferulic acid. J. Neurochem. 89: 2004; 484–493