GSE197199 Genome-wide analysis of gene expression in brain of Neil3-deficient Alzheimer's disease mouse model

Contributors : Milena A Egiazarian ; Silje St ømstad ; Teri Sakshaug ; Ana B Nescolarde ; Nicole Bethge ; Magnar Bjørås ; Katja SchefflerSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusOxidative stress generating DNA damage has been shown to be a key characteristic in Alzheimer ’s disease (AD). However, how it affects the pathogenesis of AD is not yet fully understood. NEIL3 is a DNA glycosylase initiating oxidative DNA repair and with a distinct expression pattern in proliferating cells. In brain, its function has been linked to hippocampal-dependent memory and to induc tion of neurogenesis after stroke and in prion disease. Here, we generated a novel AD mouse model deficient for Neil3 to study the impact of impaired oxidative base lesion repair on the pathogenesis of AD. Our results demonstrate an age-dependent decrease in amyloid-β (Aβ) plaque deposition in fem ale NEIL3-deficient AD mice. Moreover, male NEIL3-deficient AD mice show reduced neural stem cell proliferation in the adult hippocampus and impaired working memory. These effects seem to be independent of DNA repair as both sexes show increased level of oxidative base lesions in the hippocampus upo n loss of NEIL3. Thus, our findings suggest a sex-dependent role of NEIL3 in the progression of AD by altering cerebral Aβ accumulation and promoting adult hippocampal neurogenesis to maintain cognitive function.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research