Transcriptomic Insights into the Response of the Olfactory Bulb to Selenium Treatment in a Mouse Model of Alzheimer’s Disease

Abstract

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 Fabp7, Evt5 and Gal; some are involved in improving cognition and memory, such as Areg; and some are involved in anti-oxidative stress and anti-apoptosis, such as Adcyap1 and Scg2. The downregulated genes are mainly associated with inflammation and apoptosis, such as Lrg1, Scgb3a1 and Pglyrp1. 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.

Toxicology and pharmacology of synthetic organoselenium compounds: an update

“…In particular, selenomethionine is the naturally occurring organoselenium most studied in models of AD (Attaran et al 2020 ; Zhang et al 2016a , 2018 ; Zheng et al 2017a ); its effects include increase of neurogenesis, reduction of Aβ, tau hyperphosphorylation, and neurofibrillary tangles formation, tau autophagic clearance, activation of glial cells, and regulation of metal dyshomeostasis, thereby improving learning and memory (Song et al 2014 ; Xie et al 2018b ; Zhang et al 2016b , 2017a , b ; Zheng et al 2019a ).…”

Ocimum basilicum (Basil) Modulates Apoptosis and Neurogenesis in Olfactory Pulp of Mice Exposed to Chronic Unpredictable Mild Stress

“…The laminar organization of olfactory bulb combines a unique neuronal morphology and complex synaptic connections which play a basic role in smell perception and modify the response of the output neurons for sharp tuning of a given odor ( 29 ). Olfactory dysfunction is considered a premotor sign of neurodegeneration that appears early in the degenerative process as in Alzheimer disease and Parkinson disease ( 30 , 31 ). Moreover, the olfactory bulbectomy of rats has been validated as a model of depression over the past 30 years, suggesting a close relationship between MOB and depression ( 15 – 17 ).…”

Musk (Moschus moschiferus) Attenuates Changes in Main Olfactory Bulb of Depressed Mice: Behavioral, Biochemical, and Histopathological Evidence

“…The link between olfactory function and depression has been established. Many studies reported that decline in olfactory functions is the earliest biological marker of motor dysfunction or cognitive impairments appearing in the neurodegenerative disorders such as that occurs in Parkinson disease and Alzheimer disease (Meyer et al, 2018;Zheng et al, 2019). In this study, we hypothesized that inhalation of musk improves CUMS-induced structural changes in MOB.…”