Institute of Histology and Embryology "Aleksandar Đ Kostić", School of Medicine, University of Belgrade, Belgrade, Serbia.
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
J Alzheimers Dis. 2018;65(3):963-976. doi: 10.3233/JAD-180277.
Dysregulation of neurogenesis in the subgranular zone (SGZ) of the hippocampal dentate gyrus has been related to cognitive deficits and memory loss in neurodegenerative diseases, such as Alzheimer's disease (AD). Members of the B group of SOX transcription factors play critical roles in regulating neurogenesis in the embryonic and adult nervous system, including maintaining the multipotency, renewal, and cell fate decision of neural stem/progenitor cells. The aim of the present study was to evaluate the expression patterns of selected SOXB proteins in the SGZ, of 8-week-old male and female 5xFAD mice, which represent a transgenic model of AD with a severe and very early development of amyloid pathology. Immunohistochemical analysis showed a significant decrease in the number of cells expressing SOX1, SOX2, and SOX21 transcription factors within the SGZ of 5xFAD mice in comparison to their non-transgenic counterparts which coincidences with reduced number of doublecortin immunoreactive immature neurons found in Tg males. Despite observed changes in expressional pattern of examined SOXB proteins, the proliferative capacity evaluated by the number of Ki-67 immunoreactive cells remained unaffected in transgenic mice of both genders. Based on our results, we suggest that SOXB proteins might be considered as new biomarkers for the detection of early impairments in adult neurogenesis in different animal models or/and new targets in human regenerative medicine.
脑区颗粒下区（SGZ）中的神经发生失调与神经退行性疾病（如阿尔茨海默病（AD））中的认知缺陷和记忆丧失有关。SOX 转录因子 B 组的成员在胚胎和成人神经系统中的神经发生中发挥着关键作用，包括维持神经干细胞/祖细胞的多能性、更新和细胞命运决定。本研究旨在评估选定的 SOXB 蛋白在 SGZ 中的表达模式，在 8 周龄雄性和雌性 5xFAD 小鼠中，5xFAD 小鼠代表了一种具有严重和早期淀粉样病理学发展的 AD 转基因模型。免疫组织化学分析显示，与非转基因对照相比，5xFAD 小鼠 SGZ 中表达 SOX1、SOX2 和 SOX21 转录因子的细胞数量显著减少，与 Tg 雄性中发现的双皮质素免疫反应性未成熟神经元数量减少相一致。尽管观察到所检查的 SOXB 蛋白的表达模式发生变化，但通过 Ki-67 免疫反应性细胞的数量评估的增殖能力在两种性别的转基因小鼠中均未受到影响。基于我们的结果，我们认为 SOXB 蛋白可以被认为是检测不同动物模型中成年神经发生早期损伤的新生物标志物，或者是人类再生医学中的新靶标。
