title: AMPK activation ameliorates Alzheimer's disease-like pathology and spatial memory impairment in a streptozotocin-induced Alzheimer's disease model in rats.
abstract: Collecting evidence has shown that type 2 diabetes mellitus is a high risk factor of late-onset Alzheimer's disease (AD); the energy metabolic dysfunction is thought to be a convergent point of the two diseases. However, the underlying mechanisms of diabetes-associated AD are still unclear. In the current study, we investigated the roles of AMPK in diabetes-related AD-like pathologic features in models of intracerebroventricular-streptozotocin (ICV-STZ) animals. Rats infused with STZ (3 mg/kg, once) were followed by injection of AICAR (AMPK activator) or vehicle via ICV. We found that the level of p-AMPK (active type of AMPK) and SIRT1 activity were decreased and the level of phosphorylated tau was increased at Ser396 and Thr231 sites in ICV-STZ rats when compared with control rats. Mitochondria from ICV-STZ rats displayed a significant decrease in mitochondrial membrane potential, complex I activity, ATP level, and superoxide dismutase activity as well as an increase of reactive oxygen species production when compared with that from control rats. Meanwhile the number of apoptotic cell confirmed by cleaved caspase-3 (active type of caspase-3) staining was also stronger in ICV-STZ rats than control rats. All pathological changes including biochemistry and cognitive function could be mitigated through rescuing AMPK activity with its specific activator (AICAR) in ICV-STZ rats. Taken together, these results suggested that AMPK activation improves AD-like pathological changes via repairing mitochondrial functions in ICV-STZ rats.
authors.affiliation: Key Laboratory of Neurological Diseases of Education Ministry, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Lai-Ling
authors.initials: LL
authors.lastname: Du
authors.affiliation: Key Laboratory of Neurological Diseases of Education Ministry, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Da-Min
authors.initials: DM
authors.lastname: Chai
authors.affiliation: Key Laboratory of Neurological Diseases of Education Ministry, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Neurological Diseases of Education Ministry, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Li
authors.affiliation: Key Laboratory of Neurological Diseases of Education Ministry, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Fu-Chi
authors.initials: FC
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Neurological Diseases of Education Ministry, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Neurological Diseases of Education Ministry, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Lv-Bin
authors.initials: LB
authors.lastname: Liu
authors.affiliation: Key Laboratory of Neurological Diseases of Education Ministry, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Kang
authors.initials: K
authors.lastname: Wu
authors.affiliation: Key Laboratory of Neurological Diseases of Education Ministry, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Key Laboratory of Neurological Diseases of Education Ministry, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: Key Laboratory of Neurological Diseases of Education Ministry, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Xin-Wen
authors.initials: XW
authors.lastname: Zhou
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000494:pharmacology; D065852:Spatial Memory / Q000187:drug effects* / Q000502:physiology; D013311:Streptozocin; D016875:tau Proteins / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D012265:Ribonucleotides; D016875:tau Proteins; D000620:Aminoimidazole Carboxamide; D013311:Streptozocin; D000263:Adenylate Kinase; D053148:Caspase 3; C031143:AICA ribonucleotide
keywords: AMPK; Alzheimer's disease; diabetes mellitus; mitochondria; tau