Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China.
Int J Mol Sci. 2019 Jun 19;20(12):2998. doi: 10.3390/ijms20122998.
Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by the presence of extracellular senile plaques primarily composed of Aβ peptides and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau proteins. Olfactory dysfunction is an early clinical phenotype in AD and was reported to be attributable to the presence of NFTs, senile Aβ plaques in the olfactory bulb (OB). Our previous research found that selenomethionine (Se-Met), a major form of selenium (Se) in organisms, effectively increased oxidation resistance as well as reduced the generation and deposition of Aβ and tau hyperphosphorylation in the olfactory bulb of a triple transgenic mouse model of AD (3×Tg-AD), thereby suggesting a potential therapeutic option for AD. In this study, we further investigated changes in the transcriptome data of olfactory bulb tissues of 7-month-old triple transgenic AD (3×Tg-AD) mice treated with Se-Met (6 µg/mL) for three months. Comparison of the gene expression profile between Se-Met-treated and control mice revealed 143 differentially expressed genes (DEGs). Among these genes, 21 DEGs were upregulated and 122 downregulated. The DEGs were then annotated against the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The results show that upregulated genes can be roughly classified into three types. Some of them mainly regulate the regeneration of nerves, such as , and ; some are involved in improving cognition and memory, such as ; and some are involved in anti-oxidative stress and anti-apoptosis, such as and . The downregulated genes are mainly associated with inflammation and apoptosis, such as , and . The reliability of the transcriptomic data was validated by quantitative real time polymerase chain reaction (qRT-PCR) for the selected genes. These results were in line with our previous study, which indicated therapeutic effects of Se-Met on AD mice, providing a theoretical basis for further study of the treatment of AD by Se-Met.
阿尔茨海默病（AD）是一种破坏性的神经退行性疾病，其特征是存在细胞外老年斑，主要由 Aβ肽组成，以及由过度磷酸化的 tau 蛋白组成的细胞内神经原纤维缠结（NFTs）。嗅觉功能障碍是 AD 的早期临床表型，据报道归因于 NFTs、嗅球（OB）中的老年 Aβ斑块的存在。我们之前的研究发现，硒代蛋氨酸（Se-Met），生物体内硒的主要形式，有效地增加了抗氧化能力，同时减少了 AD 三转基因小鼠模型（3×Tg-AD）嗅球中 Aβ和 tau 过度磷酸化的产生和沉积，从而为 AD 提供了一种潜在的治疗选择。在这项研究中，我们进一步研究了用 Se-Met（6 µg/mL）处理三个月的 7 个月大的三转基因 AD（3×Tg-AD）小鼠嗅球组织的转录组数据的变化。比较 Se-Met 处理组和对照组小鼠的基因表达谱，发现 143 个差异表达基因（DEGs）。其中，21 个基因上调，122 个基因下调。这些 DEGs 随后被注释到基因本体论（GO）和京都基因与基因组百科全书（KEGG）数据库中。结果表明，上调的基因大致可以分为三类。其中一些主要调节神经再生，如、和；一些参与改善认知和记忆，如；还有一些参与抗氧化应激和抗细胞凋亡，如和。下调的基因主要与炎症和细胞凋亡有关，如、和。通过对选定基因进行定量实时聚合酶链反应（qRT-PCR）验证了转录组数据的可靠性。这些结果与我们之前的研究一致，表明 Se-Met 对 AD 小鼠有治疗作用，为进一步研究 Se-Met 治疗 AD 提供了理论基础。
