title: Combination of PPT with LiCl Treatment Prevented Bilateral Ovariectomy-Induced Hippocampal-Dependent Cognition Deficit in Rats.
abstract: Estrogen deprivation is a high risk of cognitive dysfunction in neurodegenerative diseases, and the early used estrogen replacement has been proved effective in many studies. Because of the adverse actions, selective estrogen receptor modulating has been raised to substitute for estrogen replacement. In this study, we observed in hippocampus of bilaterally ovariectomized rats that the level of estrogen receptor α (ERα) was decreased in nuclei with activated glycogen synthase kinase-3β (GSK-3β) in cytoplasm at 8 weeks after operation. The level of nuclear ERα is important for its transcriptional property, and the inhibition of GSK-3β benefits to ERα nuclear translocation. Then, we used 4,4k,4a-(4-propyl-[1H]-pyrazole-1, 3, 5-triyl) trisphenol (PPT) (1 mg/kg/day), an agonist of ERα, combined with LiCl (40 mg/kg/day), an inhibitor of GSK-3β, to treat the ovariectomized rats. After the combination treatment of these two drugs (PPT + LiCl), the improved learning and memory abilities of ovariectomized rats in Morris water maze, increased dendritic spines in CA1 region, and decreased tau phosphorylation at Ser-396 in hippocampus were observed. Furthermore, PPT + LiCl treatment significantly increased ERα level in the nuclear fraction of hippocampus, and in the cytoplasmic fraction, the total level of GSK-3β was declined after treatment with its increased phosphorylation at Ser-9 (inactivation form). This study suggested that PPT + LiCl treatment could inhibit the activation of cytoplasmic GSK-3β and promote the nuclear translocation of ERα, and ERα together with GSK-3β maybe the targets to preserve hippocampus-dependent cognitive ability after long-term ovariectomy.
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Institute for Brain Research, Huazhong University of Science and Technology, Hangkong Road 13#, Wuhan, 430030, China.|Department of Neurology, Liyuan Hospital, Huazhong University of Science and Technology, East Lake Ecological Scenic Lake road 39#, Wuhan, 430077, China.|Affiliated Mental Health Centre, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Na
authors.initials: N
authors.lastname: Qu
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Institute for Brain Research, Huazhong University of Science and Technology, Hangkong Road 13#, Wuhan, 430030, China.|Department of Neurology, Liyuan Hospital, Huazhong University of Science and Technology, East Lake Ecological Scenic Lake road 39#, Wuhan, 430077, China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Zhou
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Institute for Brain Research, Huazhong University of Science and Technology, Hangkong Road 13#, Wuhan, 430030, China.|Department of Neurology, Liyuan Hospital, Huazhong University of Science and Technology, East Lake Ecological Scenic Lake road 39#, Wuhan, 430077, China.
authors.forename: Li
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Institute for Brain Research, Huazhong University of Science and Technology, Hangkong Road 13#, Wuhan, 430030, China.|Department of Neurology, Liyuan Hospital, Huazhong University of Science and Technology, East Lake Ecological Scenic Lake road 39#, Wuhan, 430077, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Institute for Brain Research, Huazhong University of Science and Technology, Hangkong Road 13#, Wuhan, 430030, China.|Department of Neurology, Liyuan Hospital, Huazhong University of Science and Technology, East Lake Ecological Scenic Lake road 39#, Wuhan, 430077, China.
authors.forename: Jia-Xin
authors.initials: JX
authors.lastname: Xu
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Institute for Brain Research, Huazhong University of Science and Technology, Hangkong Road 13#, Wuhan, 430030, China.|Department of Neurology, Liyuan Hospital, Huazhong University of Science and Technology, East Lake Ecological Scenic Lake road 39#, Wuhan, 430077, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Institute for Brain Research, Huazhong University of Science and Technology, Hangkong Road 13#, Wuhan, 430030, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chu
authors.affiliation: Department of Neurology, Liyuan Hospital, Huazhong University of Science and Technology, East Lake Ecological Scenic Lake road 39#, Wuhan, 430077, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Institute for Brain Research, Huazhong University of Science and Technology, Hangkong Road 13#, Wuhan, 430030, China.
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Institute for Brain Research, Huazhong University of Science and Technology, Hangkong Road 13#, Wuhan, 430030, China. zhangqi@mails.tjmu.edu.cn.|Department of Neurology, Liyuan Hospital, Huazhong University of Science and Technology, East Lake Ecological Scenic Lake road 39#, Wuhan, 430077, China. zhangqi@mails.tjmu.edu.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Institute for Brain Research, Huazhong University of Science and Technology, Hangkong Road 13#, Wuhan, 430030, China. tianq@hust.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018021:Lithium Chloride / Q000494:pharmacology / Q000627:therapeutic use*; D018782:Maze Learning / Q000187:drug effects; D010052:Ovariectomy / Q000009:adverse effects*; D010636:Phenols / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D047628:Estrogen Receptor alpha; D010636:Phenols; D011720:Pyrazoles; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D010768:Phosphoserine; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride
keywords: Estrogen receptor α; Glycogen synthase kinase-3β; Ovariectomy