title: Treatment effects of tanshinone IIA against intracerebroventricular streptozotocin induced memory deficits in mice.
abstract: Our previous studies demonstrated that tanshinone IIA (tan IIA) has significant protective effects against the neurotoxicity induced by β-amyloid protein (Aβ) in cultured cortical neurons and PC12 cells. This study was designed to investigate the protective effects of tan IIA against memory deficits induced by streptozotocin (STZ) in a model of sporadic Alzheimer's disease (AD). STZ was injected twice intracerebroventrically (3mg/kg ICV) on alternate days (day 1 and day 3) in mice. Daily treatment with tan IIA (20, 40, and 80mg/kg, i.g.) starting from the first dose of STZ for 28 days showed a dose dependent improvement in STZ induced memory deficits as assessed by Morris water maze (MWM) test. Nissl staining results confirmed the protective effects of tan IIA on cerebral cortical and hippocampal neurons damage induced by STZ. In addition, tan IIA markedly reduced STZ induced elevation in acetylcholinesterase (AChE) activity and malondialdehyde (MDA) level, and significantly inhibited STZ induced reduction in superoxide dismutases (SOD) and glutathione peroxidase (GSH-Px) activities in the parietal cortex and hippocampus. Moreover, tan IIA attenuated p38 mitogen activated protein kinase (MAPK) phosphorylation in the parietal cortex and hippocampus. These findings demonstrate that tan IIA prevents STZ induced memory deficits may be attributed to ameliorating neuronal damage, restoring cholinergic function, attenuating oxidative stress and blocking p38 MAPK signal pathway activation. Based on our previous studies, the present study provides further support for the potential use of tan IIA in the treatment of AD.
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Youxuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zha
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Mengping
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Guangde
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Kaige
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Neurology, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Yulang
authors.initials: Y
authors.lastname: Fei
authors.affiliation: Center of Morphology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Yaojie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China. Electronic address: wn_yang@mail.xjtu.edu.cn.
authors.forename: Weina
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China. Electronic address: qianyh38@mail.xjtu.edu.cn.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Qian
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D057967:Infusions, Intraventricular; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010296:Parietal Lobe / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D011897:Random Allocation; D013311:Streptozocin / Q000008:administration & dosage; D013482:Superoxide Dismutase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D045784:Abietanes; D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; C021751:tanshinone; D008315:Malondialdehyde; D013311:Streptozocin; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase; Memory deficits; Oxidative stress; Streptozotocin; Tanshinone IIA