Selenomethionine Ameliorates Neuropathology in the Olfactory Bulb of a Triple Transgenic Mouse Model of Alzheimer's Disease.
Olfactory dysfunction is an early and common symptom in Alzheimer's disease (AD) and is reported to be related to several pathologic changes, including the deposition of Aβ and hyperphosphorylated tau protein as well as synaptic impairment. Selenomethionine (Se-Met), the major form of selenium in animals and humans, may be a promising therapeutic option for AD as it decreases the deposition of Aβ and tau hyperphosphorylation in a triple transgenic mouse model of AD (3× Tg-AD). In this study, 4-month-old AD mice were treated with 6 µg/mL Se-Met in drinking water for 12 weeks and the effect of Se-Met on neuropathological deficits in olfactory bulb (OB) of 3× Tg-AD mice was investigated. The administration of Se-Met effectively decreased the production and deposition of Aβ by inhibiting β-site amyloid precursor protein cleaving enzyme 1 (BACE1)-regulated amyloid precursor protein (APP) processing and reduced the level of total tau and phosphorylated tau, which depended on depressing the activity and expression of glycogen synthase kinase-3β(GSK-3β) and cyclin-dependent kinase 5 (CDK5). Meanwhile, Se-Met reduced glial activation, relieved neuroinflammation and attenuated neuronal cell death in the OB of AD mice. So Se-Met could improve pathologic changes of AD in the OB, which further demonstrated the potential therapeutic effect of Se-Met in AD.
Changchun Institute of Applied Chemistry, University of Chinese Academy of Sciences, Changchun 130022, China. zhangzhonghao@email.szu.edu.cn.
Zhong-Hao
ZH
Zhang
Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China. chenchen198951@163.com.
Chen
C
Chen
Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China. happy_wuqiuyan@126.com.
Qiu-Yan
QY
Wu
Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China. zhengrui_210@163.com.
Rui
R
Zheng
Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China. yaochen913@163.com.
Yao
Y
Chen
Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China. liuqiong@szu.edu.cn.
Qiong
Q
Liu
Changchun Institute of Applied Chemistry, University of Chinese Academy of Sciences, Changchun 130022, China. jzni@szu.edu.cn.|Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China. jzni@szu.edu.cn.
Jia-Zuan
JZ
Ni
Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China. lilys@szu.edu.cn.
Guo-Li
GL
Song
Alzheimer’s disease; CDK5; olfactory dysfunction; selenomethionine; tau
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