TRANSGENIC MICE MODEL OF ALZHEIMER’S DISEASE: EARLY CHANGES IN THE NEUROGENESIS IN THE SUBGRANULAR ZONE OF THE HIPPOCAMPUS

Аннотация

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Background. Dysregulation of neurogenesis in the subgranular zone (SGZ) of the hippocampus has been related to cognitive deficits and memory loss in neurodegenerative diseases, such as Alzheimer’s disease (AD). Transgenic (Tg) 5xFAD mice represent a model of Alzheimer’s disease characterized by an early deposition of amyloid plaques. SoxB transcriptional factor regulate different cellular processes during embryonic and adult neurogenesis, but their roles in neurodegenerative disorders is not fully understood. Aim. The aim of this study was to characterize the early changes in hippocampal neurogenesis in 8 weeks old 5xFAD Tg mice and to investigate the expression of SoxB transcriptional factors. Material and Methods. Transgenic male mice and their respective non-transgenic controls were used in the present study. Results and Discussion. Proliferating cells and immature neurons were detected by immunohistochemical expression of Ki67 and doublecortin (DCX), while neuronal stem/precursor cells were identified by the expression of Sox 1, Sox 2 and Sox21. Immunohistochemical analysis showed that 5xFAD mice in the SGZ of the hippocampus have significantly lower numbers of Sox 1, Sox21 and DCX immunoreactive cells, while the number of proliferating cells was unchanged when compared to their non-transgenic controls. The results of our study show that early changes in the neurogenesis in 5xFAD animal model occur despite the preserved proliferative potential in the SGZ, and clearly indicate for the first time that SoxB transcriptional factors are affected during this process.