title: Steroid sulfatase inhibitor DU-14 protects spatial memory and synaptic plasticity from disruption by amyloid β protein in male rats.
abstract: Alzheimer's disease (AD) is an age-related mental disorder characterized by progressive loss of memory and multiple cognitive impairments. The overproduction and aggregation of Amyloid β protein (Aβ) in the brain, especially in the hippocampus, are closely involved in the memory loss in the patients with AD. Accumulating evidence indicates that the Aβ-induced imbalance of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) in the brain plays an important role in the AD pathogenesis and progression. The level of DHEA is elevated, while DHEAS is dramatically decreased in the AD brain. The present study tried to restore the balance between DHEA and DHEAS by using a non-steroidal sulfatase inhibitor DU-14, which increases endogenous DHEAS through preventing DHEAS converted back into DHEA. We found that: (1) DU-14 effectively attenuated the Aβ1-42-induced cognitive deficits in spatial learning and memory of rats in Morris water maze test; (2) DU-14 prevented Aβ1-42-induced decrease in the cholinergic theta rhythm of hippocampal local field potential (LFP) in the CA1 region; (3) DU-14 protected hippocampal synaptic plasticity against Aβ1-42-induced suppression of long term potentiation (LTP). These results provide evidence for the neuroprotective action of DU-14 against neurotoxic Aβ, suggesting that up-regulation of endogenous DHEAS by DU-14 could be beneficial to the alleviation of Aβ-induced impairments in spatial memory and synaptic plasticity.
authors.affiliation: Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, PR China; Department of Clinical Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300100, PR China.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Yue
authors.affiliation: Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Jia-Qing
authors.initials: JQ
authors.lastname: Tong
authors.affiliation: Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Zhao-Jun
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300100, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Liu
authors.affiliation: Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Cai
authors.affiliation: Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: jinshunqi2009@163.com.
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Qi
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D003072:Cognition Disorders / Q000378:metabolism / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000517:prevention & control; D009473:Neuronal Plasticity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects*; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors*; D014439:Tyramine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C103321:4-O-(sulfamoyl)-N-tetradecanoyltyramine; D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D043266:Steryl-Sulfatase; D014439:Tyramine
keywords: Amyloid β protein; DU-14; Dehydroepiandrosterone sulfate; Long term potentiation; Spatial memory; Synaptic plasticity; Theta rhythm