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P1‐151: The use of in vitro models of neurodegeneration to screen for lipid biomarkers in Alzheimer's disease
Author(s) -
Biggs Thelma E.,
Ledger Vikki,
Foreman Janet,
Pringle Ashley,
Sundstrom Lars,
Consortium AddNeuroMed
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.739
Subject(s) - neurodegeneration , oxidative stress , hippocampal formation , in vitro , isoprostane , chemistry , isoprostanes , pharmacology , biochemistry , disease , biology , neuroscience , medicine , lipid peroxidation
through Dkk-1 via the activation of p53. Methods: We sort to further examine the relationship between wnt signalling, A, and p53. We performed two separate microarray experiments using mouse primary cortical neurons grown in culture for seven days, treated either with mouse Dkk-1 recombinant protein (800 ng/ml), or a peptide corresponding to A25-35 (20 M), for two hours. Total RNA was extracted and hybridized to Affymetrix microarrays. We and also generated a Dkk-1 transgenic (TG) mouse expressing murine Dkk-1 driven by the murine prion promoter, resulting in increased expression, post development, in temporal regions of the brain. Results: Following stringent statistical analyses gene lists were generated from the two treatments and compared. Remarkably, after applying a 1.5 fold change cut off to the lists, within the top seven most significantly changing genes, 4 were common to the two treatements; Egr1, Cyclin D1, NAB2 and Klf10. We then measured the expression of these genes in temporal cortex of neonatal Dkk-1 TG mice. The expression of all four genes was also in creased in TGs compared to their litter mate controls. Developmentally the Dkk-1 TG mice appeared normal. Conclusions: The similarity in the gene lists obtained from the microarray experiments using two different treatments supports the contention that A is able to activate p53, which in turn increases the expression of Dkk-1. As these same genes are also up-regulated in neonatal Dkk-1 TG brain we are now aging Dkk-1 TG mice to determine if chronic over expression of these genes leads to signs of Alzheimer’s like neuropathology.