| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2041638 | Cell Reports | 2012 | 8 Pages |
SummaryAccumulation of oxidative DNA damage has been proposed as a potential cause of age-related cognitive decline. The major pathway for removal of oxidative DNA base lesions is base excision repair, which is initiated by DNA glycosylases. In mice, Neil3 is the main DNA glycosylase for repair of hydantoin lesions in single-stranded DNA of neural stem/progenitor cells, promoting neurogenesis. Adult neurogenesis is crucial for maintenance of hippocampus-dependent functions involved in behavior. Herein, behavioral studies reveal learning and memory deficits and reduced anxiety-like behavior in Neil3−/− mice. Neural stem/progenitor cells from aged Neil3−/− mice show impaired proliferative capacity and reduced DNA repair activity. Furthermore, hippocampal neurons in Neil3−/− mice display synaptic irregularities. It appears that Neil3-dependent repair of oxidative DNA damage in neural stem/progenitor cells is required for maintenance of adult neurogenesis to counteract the age-associated deterioration of cognitive performance.
Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Neural stem/progenitor cells from Neil3−/− mice have reduced proliferation capacity ► NEIL3-deficient mice display reduced anxiety and impaired learning and memory ► Repair of hydantoin lesions in DNA is diminished in Neil3−/− neurospheres ► Synaptic structure and receptor contents are anomalous in Neil3−/− mice
