title: Treatment effects of Cardiotrophin-1 (CT-1) on streptozotocin-induced memory deficits in mice.
abstract: Increasing evidence has shown that diabetes-associated cognitive impairment is correlated with mitochondrial dysfunction and resultant synaptic injury as well as brain insulin resistance. Cardiotrophin-1 (CT-1), a regulator of energy metabolism, has been shown to exhibit impressive neuroprotective effects. In this study, we evaluated the effects of CT-1 on brain pathological features in intracerebroventrical-streptozotocin (ICV-STZ)-treated mouse model, and explored its potential mechanisms. STZ was injected twice (3mg/kg, ICV) on alternate days (day 1 and day 3) in mice. Daily treatment with CT-1 (1μg/day, ICV) starting from the first dose of STZ for 14days showed that CT-1 significantly improved learning and memory deficits, alleviated mitochondrial dysfunction, and increased synaptic density in the CA1 region of the hippocampus in ICV-STZ-treated mice. Moreover, CT-1 significantly enhanced insulin signaling pathway in the hippocampus of ICV-STZ-treated mice when compared with the control. However, all the protective effects including biochemistry, pathological changes and cognitive function could be blocked by an ICV injection of Compound C, a specific AMPK inhibitor. Taken together, these results suggested that CT-1 improves pathological changes and cognitive impairments via AMPK activation in ICV-STZ mice.
authors.affiliation: Department of Pathogen Biology, Medical College, Henan University of Science and Technology, Luoyang, China. Electronic address: wangdongmei@haust.edu.cn.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Immunology, Medical College, Henan University of Science and Technology, Luoyang, China.
authors.forename: Xiaozhuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang, China.
authors.forename: Guomin
authors.initials: G
authors.lastname: Shen
authors.affiliation: Department of Pathogen Biology, Medical College, Henan University of Science and Technology, Luoyang, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang, China.
authors.forename: Sanqiang
authors.initials: S
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors; D000818:Animals; D001921:Brain / Q000473:pathology*; D003071:Cognition / Q000187:drug effects; D060825:Cognitive Dysfunction / Q000188:drug therapy*; D016207:Cytokines / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D007328:Insulin / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015398:Signal Transduction; D013311:Streptozocin
chemical_list: D016207:Cytokines; D007328:Insulin; D018696:Neuroprotective Agents; D013311:Streptozocin; C092073:cardiotrophin 1; D055372:AMP-Activated Protein Kinases
keywords: AMPK; CT-1; Insulin signal; Mitochondrial dysfunction; Streptozotocin