| dc.description.abstract | DNA damage can be caused through exposure to both exogenous and endogenous agents. Through by-products of physiological cellular processes neurons are constantly exposed to agents that can induce DNA base lesions. Base excision repair (BER), initiated through the action of DNA glycosylases, primarily recognizes DNA base lesions and maintains genomic stability, thus preventing accumulation of potential mutations. Alkyladenine DNA glycosylase (AAG) initiates BER by recognizing and removing a wide variety of alkylated bases. In addition to its function in DNA repair, we have shown that AAG impacts transcription and our preliminary work indicates that loss of Aag in mice influences behaviour. One brain area important in behaviour and cognition is the hippocampus. Through transcriptomics analysis, our unpublished results suggest that Aag regulates the transcription of genes within the hippocampus, such as aldehyde dehydrogenase 2 (Aldh2) and gamma-aminobutyric acid receptor subunit alpha-2 (Gabra2). While Aag could influence hippocampal functioning and gene expression, to which extent loss of Aag influences its cellular organization remains unknown. Here, immunofluorescence and confocal microscopy were used to investigate the impact of Aag DNA glycosylase on the development and cytoarchitecture of the mouse hippocampus at postnatal day 5 (P5). Hippocampi of mice lacking Aag (Aag-/-) showed significantly increased numbers of Ki67+ proliferating cells and less DNA double stranded breaks, indicated by the number of γH2AX foci, than the WT counterparts. Though not significant, the number of neural stem cells was reduced, while the numbers of mature neurons increased, and slightly higher intensity of Aldh2 signal was detected in Aag-/- compared to WT hippocampi. There was no difference in signal intensities of Map2, Gfap, Gabra2, or 5hmC between the groups. These results suggest that Aag may play a role in the development of the hippocampus at age P5, as well as could be involved in adult neurogenesis, transcription and genomic stability in mice. | en |