title: The ameliorating effects of stigmasterol on scopolamine-induced memory impairments in mice.
abstract: Stigmasterol, a kind of phytosterol, is present in small amounts in various foods. In the present study, we investigated the effects of stigmasterol on scopolamine-induced memory impairments using the passive avoidance and the Morris water maze tasks in mice. In addition, changes in memory-related molecules, including extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB), were examined following the administration of stigmasterol. Scopolamine-induced memory impairments were significantly attenuated by the administration of stigmasterol (10mg/kg) in the passive avoidance task. In the Morris water maze task, the escape latencies were significantly decreased in the stigmasterol-treated group compared to the scopolamine-treated group during the training phase. The swimming times within the target zone during the probe trial were significantly increased as compared to scopolamine-treated mice. Furthermore, the ameliorating effect of stigmasterol on scopolamine-induced memory dysfunction was blocked by a sub-effective dose of dizocilpine (MK-801), an NMDA receptor antagonist, and tamoxifen, an estrogen receptor antagonist, in the passive avoidance task. In addition, the expression levels of phosphorylated ERK and CREB in the hippocampus were significantly increased by stigmasterol, which was blocked by tamoxifen or MK-801 with scopolamine. These results suggest that stigmasterol-induced cognitive ameliorative effects are mediated by the enhancement of cholinergic neurotransmission system via the activation of estrogen or NMDA receptors.
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Jun Man
authors.initials: JM
authors.lastname: Jung
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Mudan
authors.initials: M
authors.lastname: Cai
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Liu
authors.forename: Jin Gyu
authors.initials: JG
authors.lastname: Hong
authors.forename: Chang Hwan
authors.initials: CH
authors.lastname: Lee
authors.forename: Kang Ro
authors.initials: KR
authors.lastname: Lee
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008813:Mice, Inbred ICR; D010766:Phosphorylation / Q000187:drug effects; D012601:Scopolamine / Q000009:adverse effects*; D013265:Stigmasterol / Q000494:pharmacology* / Q000627:therapeutic use; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D013629:Tamoxifen; D016291:Dizocilpine Maleate; D013265:Stigmasterol; D012601:Scopolamine; D048049:Extracellular Signal-Regulated MAP Kinases