Stressful learning paradigm precludes manifestation of cognitive ability in sphingomyelin synthase-2 knockout mice
Stressful learning paradigm precludes manifestation of cognitive ability in sphingomyelin synthase-2 knockout mice
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DOI：
10.1016/j.bbr.2016.11.010
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发表时间：
2017-02
影响因子：
2.7
通讯作者：
Min Wang;O. Uchiumi;H. Ogiso;Yuan Shui;Jingyu Zou;Chieko Hashizume;M. Taniguchi;T. Okazaki;N. Kato
中科院分区：
文献类型：
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作者：
Min Wang;O. Uchiumi;H. Ogiso;Yuan Shui;Jingyu Zou;Chieko Hashizume;M. Taniguchi;T. Okazaki;N. Kato
鞘磷脂酶（SMS）是将神经酰胺转化为鞘磷脂的酶。归因于其破坏的行为表型尚未得到很好的描述。我们研究了学习能力和海马突触可塑性的小鼠在SMS2缺陷（SMS2 KO）。在情境依赖性恐惧学习和新物体识别测试中，在SMS2 KO和野生型（WT）小鼠中没有检测到学习能力的差异。相比之下，Morris水迷宫（MWM）测试的成绩在SMS2 KO小鼠中恶化。在海马CA1区，虽然基本的突触传递是正常的，短期和长期的突触可塑性适度抑制。我们解释说，MWM测试发生在潮湿的环境中可能代表的学习范式下更紧张的条件下比那些在干燥的条件下进行，和SMS2基因敲除小鼠的学习能力未能充分体现在紧张的情况下。一致的是，强迫游泳更容易在SMS2 KO小鼠中诱导抑郁样行为。质谱分析表明，神经酰胺在SMS2 KO小鼠海马中的物质分布略有改变。这些发现支持了神经酰胺合成改变的提议，神经酰胺是SMS2的底物，因此预计在SMS2 KO小鼠中进行修饰，与动物模型中的抑郁样倾向和人类抑郁症相关。
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.