Neuronal Death, Proinflammatory Cytokines and Amyloid Precursor Protein: Studies on Staggerer Mutant Mice
In Alzheimer’s, disease (AD), a combination of genetic predisposition and environmental factors may contribute to changes in β-amyloid precursor protein (APP) expression, β-amyloid deposition and neuronal loss. Head injury and acute infection that triggers inflammatory processes are known to be risk factors. In the present in vivo study we show that peripheral endotoxin injection induces a phasic increase of IL-lβ and IL-6 mRNA in mouse cerebellum, followed within 24 hours by an increase in the APPKPI/APP-695 ratio. In the cerebellum of the staggerer mouse mutant, where a severe deficit of Purkinje and granule cells occurs, elevated basal levels of IL-lβ and IL-6 mRNA and an increase in the APP-KPI/APP-695 ratio compared to wild type mice was observed. LPS stimulation further accentuated these differences for cytokines and APP isoforms. Our in vivo studies suggest that interaction loops between cytokines and APP could play an important role in the regulation of APP expression in degenerating Alzheimer’s disease brain tissue.
KeywordsWild Type Mouse Purkinje Cell Down Syndrome Staggerer Mouse Staggerer Mutant
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- Bendotti C, Forloni GL, Morgan R, O’hara BF, Oster-Granite ML, Reeves RH, Gearhart JD, Coyle JT (1988) Neuroanatomical localization and quantification of amyloid precursor protein mRNA by in situ hybridization in the brain of normal, aneuploid and lesioned mice. Proc Natl Acad Sci USA 85: 3628–3632PubMedCrossRefGoogle Scholar
- Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of Apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261: 921–923Google Scholar
- Goate A, Chartier-Harlin M-C, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, Mant R, Newton P, Rocke K, Roques P, Talbot C, Pericak-Vance M, Roses A, Williamson R, Rossor M, Owen M, Hardy J (1991) Segregation of a missence mutation in the amyloid precursor gene with familial Alzheimer’s disease. Nature 349: 704–706PubMedCrossRefGoogle Scholar
- Maniatis T, Fritch EF, Sambrook J (1987) Molecular cloning A laboratory manual. Cold Spring Harbor LaboratoryGoogle Scholar
- Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davies D, Sinna S, Schlossmacher M, Whaley J, Swindlehurst C, McCormack R, Wolfert R, Selkoe D, Lieberburg I, Schenk D (1992) Isolation and quantification of soluble Alzheimer’s β -peptide from biological fluids. Nature 359: 325–227PubMedCrossRefGoogle Scholar
- Siebert, PD, Larrick JW (1992) PCR MIMICS — Competitive DNA fragments for use as internal standards in quantitative PCR. Bio Techniques 14: 244–249Google Scholar
- Wollman EE, Kopmels B, Bakalian A, Delhaye-Bouchaud N, Fradelizi D, Mariani J (1992) Cytokine and neuronal degeneration. In: Dantzer R, Rothwell N (eds) Cytokine and neuronal degeneration Pergamon Press Oxford, pp 187–203Google Scholar