title: Selenomethionine ameliorates cognitive decline, reduces tau hyperphosphorylation, and reverses synaptic deficit in the triple transgenic mouse model of Alzheimer's disease.
abstract: Disruption of the intracellular balance between free radicals and the antioxidant system is a prominent and early feature in the neuropathology of Alzheimer's disease (AD). Selenium, a vital trace element with known antioxidant potential, has been reported to provide neuroprotection through resisting oxidative damage but its therapeutic effect on AD remains to be investigated. The objective of our study was to investigate the potential of selenomethionine (Se-Met), an organic form of selenium, in the treatment of cognitive dysfunction and neuropathology of triple transgenic AD (3 × Tg-AD) mice. 3 × Tg-AD mice, which were four months old, were treated with Se-Met for 3 months and demonstrated significant improvements in cognitive deficit along with an increased selenium level compared with the untreated control mice. Se-Met treatment significantly reduced the level of total tau and phosphorylated tau, mitigated the decrease of synaptic proteins including synaptophysin and postsynaptic density protein 95 in the hippocampus and cortex of the 3 × Tg-AD mice. Meanwhile, glial activation in AD mice was inhibited and the level of reduced glutathione was increased in the treated mice compared with control mice. Additionally, the expression and activity of glycogen synthase kinase 3β and protein phosphatase 2A, two important enzymes involved in tau phosphorylation, were markedly decreased and increased respectively by Se-Met treatment. Thus Se-Met improves cognitive deficit in a murine model of AD, which is associated with reduction in tau expression and hyperphosphorylation, amelioration of inflammation, and restoration of synaptic proteins and antioxidants. This study provides a novel therapeutic approach for the prevention of AD.
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Guoli
authors.initials: G
authors.lastname: Song
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Zhonghao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wen
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Qingxue
authors.initials: Q
authors.lastname: Shi
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Jiazuan
authors.initials: J
authors.lastname: Ni
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D005978:Glutathione / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008822:Mice, Transgenic; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000378:metabolism; D012643:Selenium / Q000378:metabolism; D012645:Selenomethionine / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D016708:Synaptophysin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; C558298:Mapt protein, mouse; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D016708:Synaptophysin; C569015:Syp protein, mouse; D016875:tau Proteins; D012645:Selenomethionine; D038362:Glycogen Synthase Kinase 3; D051528:Guanylate Kinases; D054648:Protein Phosphatase 2; D005978:Glutathione; D012643:Selenium
keywords: Alzheimer's disease; selenomethionine; tau; transgenic mouse model