title: Magnesium protects cognitive functions and synaptic plasticity in streptozotocin-induced sporadic Alzheimer's model.
abstract: Alzheimer's disease (AD) is characterized by profound synapse loss and impairments of learning and memory. Magnesium affects many biochemical mechanisms that are vital for neuronal properties and synaptic plasticity. Recent studies have demonstrated that the serum and brain magnesium levels are decreased in AD patients; however, the exact role of magnesium in AD pathogenesis remains unclear. Here, we found that the intraperitoneal administration of magnesium sulfate increased the brain magnesium levels and protected learning and memory capacities in streptozotocin-induced sporadic AD model rats. We also found that magnesium sulfate reversed impairments in long-term potentiation (LTP), dendritic abnormalities, and the impaired recruitment of synaptic proteins. Magnesium sulfate treatment also decreased tau hyperphosphorylation by increasing the inhibitory phosphorylation of GSK-3β at serine 9, thereby increasing the activity of Akt at Ser473 and PI3K at Tyr458/199, and improving insulin sensitivity. We conclude that magnesium treatment protects cognitive function and synaptic plasticity by inhibiting GSK-3β in sporadic AD model rats, which suggests a potential role for magnesium in AD therapy.
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Bao
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhi-Hao
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: En-Jie
authors.initials: EJ
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Rong-Xi
authors.initials: RX
authors.lastname: Huang
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Di
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Meng-Zhu
authors.initials: MZ
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Li Yuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Gong-Ping
authors.initials: GP
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007274:Injections, Intraperitoneal; D007333:Insulin Resistance; D017774:Long-Term Potentiation / Q000187:drug effects*; D008278:Magnesium Sulfate / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D016875:tau Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D016875:tau Proteins; D013311:Streptozocin; D008278:Magnesium Sulfate; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3