title: Stressful learning paradigm precludes manifestation of cognitive ability in sphingomyelin synthase-2 knockout mice.
abstract: Sphingomyelin synthases (SMSs) are enzymes converting ceramide to sphingomyelin. The behavioral phenotype attributed to their disruption has not been well described. We examined learning ability and hippocampal synaptic plasticity in mice deficient in SMS2 (SMS2 KO). In context-dependent fear learning and novel object recognition test, no difference in learning ability was detected in SMS2 KO and wild-type (WT) mice. By contrast, achievement of the Morris water maze (MWM) test was deteriorated in SMS2 KO mice. In the hippocampal CA1, while the basic synaptic transmission was normal, both short- and long-term synaptic plasticity was moderately suppressed. We interpret that the MWM test taking place in wet environment may represent learning paradigm under more stressful condition than those performed in dry conditions, and that the learning ability of SMS2 KO mice failed to manifest itself fully in stressful situations. In agreement, forced swimming induced depression-like behavior more easily in SMS2 KO mice. Mass spectrometry suggested a slightly altered species distribution of ceramide in the hippocampus of SMS2 KO mice. These findings support the proposal that altered synthesis of ceramide, which is the substrate of SMS2 and therefore expected to be modified in SMS2 KO mice, is associated with depression-like tendency in animal models and depressive disorder in humans.
authors.affiliation: Department of Physiology, Kanazawa Medical University, Ishikawa, 920-0293, Japan; Medical Research Institute, Kanazawa Medical University, Ishikawa, 920-0293, Japan; Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Physiology, Kanazawa Medical University, Ishikawa, 920-0293, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Uchiumi
authors.affiliation: Department of Hematology-Immunology, Kanazawa Medical University, Ishikawa, 920-0293, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Ogiso
authors.affiliation: Department of Physiology, Kanazawa Medical University, Ishikawa, 920-0293, Japan.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shui
authors.affiliation: Department of Physiology, Kanazawa Medical University, Ishikawa, 920-0293, Japan; First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Hematology-Immunology, Kanazawa Medical University, Ishikawa, 920-0293, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Hashizume
authors.affiliation: Department of Hematology-Immunology, Kanazawa Medical University, Ishikawa, 920-0293, Japan; Medical Research Institute, Kanazawa Medical University, Ishikawa, 920-0293, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: Department of Hematology-Immunology, Kanazawa Medical University, Ishikawa, 920-0293, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Okazaki
authors.affiliation: Department of Physiology, Kanazawa Medical University, Ishikawa, 920-0293, Japan. Electronic address: kato@kanazawa-med.ac.jp.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kato
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D055592:Biophysical Phenomena / Q000235:genetics; D002518:Ceramides / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D003863:Depression / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005106:Exploratory Behavior / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D007859:Learning Disabilities / Q000235:genetics*; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics; D021641:Recognition, Psychology / Q000502:physiology; D013550:Swimming / Q000523:psychology; D017855:Transferases (Other Substituted Phosphate Groups) / Q000172:deficiency* / Q000235:genetics
chemical_list: D002518:Ceramides; D017855:Transferases (Other Substituted Phosphate Groups); C543123:Sgms2 protein, mouse
keywords: Context-dependent fear learning; Long-term potentiation; Morris water maze; Novel object recognition test; Paired-pulse facilitation; Synaptic plasticity