title: Effects of small interfering RNA targeting sphingosine kinase-1 gene on the animal model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is an age-related, progressive neurodegenerative disorder that occurs gradually and results in memory, behavior, and personality changes. Abnormal sphingolipid metabolism was reported in AD previously. This study aimed to investigate whether sphK1 could exacerbate the accumulation of amyloid protein (Aβ) and sharpen the learning and memory ability of the animal model of AD using siRNA interference. An adenovirus vector expressing small interfering RNA (siRNA) against the sphK1 gene (sphK1-siRNA) was designed, and the effects of sphK1-siRNA on the APP/PS1 mouse four weeks after treatment with sphK1-siRNA hippocampal injection were examined. SphK1 protein expression was confirmed by using Western blotting and ceramide content coupled with S1P secretion was evaluated by enzyme-linked immunosorbent assay (ELISA). Aβ load was detected by immunohistochemical staining and ELISA. Morris water maze was adopted to test the learning and memory ability of the APP/PS1 mice. A significant difference in the expression of sphK1 protein and mRNA was observed between the siRNA group and the control group. Aβ load in transfected mice was accelerated in vivo, with significant aggravation of the learning and memory ability. The sphK1 gene modulation in the Aβ load and the learning and memory ability in the animal model of AD may be important for the treatment of AD.
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.|Department of Neurology, Shandong Qianfoshan Hospital, Jinan, 250014, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Osteology, Shandong Qianfoshan Hospital, Jinan, 250014, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Neurology, Zhongshan Hospital, Xiamen University, Xiamen, 361004, China.
authors.forename: Tian-Bao
authors.initials: TB
authors.lastname: Lai
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. gangli2008@mail.hust.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Sheng-Gang
authors.initials: SG
authors.lastname: Sun
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods*; D007859:Learning Disabilities / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D008845:Microinjections; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use; D016896:Treatment Outcome; D000099157:Sphingosine Kinase
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); D034741:RNA, Small Interfering; D000099157:Sphingosine Kinase