Deficits in cognitive function and hippocampal plasticity in GM2/GD2 synthase knockout mice
Deficits in cognitive function and hippocampal plasticity in GM2/GD2 synthase knockout mice
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DOI：
10.1002/hipo.22230
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发表时间：
2014-04
期刊：
影响因子：
3.5
通讯作者：
Sha Sha-Sha;Libin Zhou;Jun Yin;Koga Takamiya;Keiko Furukawa;Kazuro Furukawa;M. Sokabe;Ling Chen
中科院分区：
文献类型：
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作者：
Sha Sha-Sha;Libin Zhou;Jun Yin;Koga Takamiya;Keiko Furukawa;Kazuro Furukawa;M. Sokabe;Ling Chen
在这项研究中，我们使用GM2/GD2合酶敲除（GM2/GD2−/−）小鼠来研究神经节苷脂“a途径”和“b途径”缺乏对认知表现和海马突触可塑性的影响。与野生型（WT）小鼠相比，8周龄GM2/GD2−/−雄性小鼠在Morris水迷宫测试中表现出更长的逃避潜伏期，在降压抑制性回避任务中表现出更短的潜伏期。GM2/GD2−/−小鼠海马切片中的Schaffer侧支- CA1突触显示epsp斜率增加，配对脉冲促进减少，表明其突触前谷氨酸释放增强。在GM2/GD2−/−小鼠中，NMDA受体（NMDAr）依赖的LTP不能被高频（100-200 Hz）破伤风或θ - burst条件刺激（CS）诱导，而NMDAr独立的LTP可以被中频CS （20-50 Hz）诱导。在GM2/GD2−/−小鼠切片中应用单涎神经节苷脂GM1特异性恢复a通路，可阻止突触前谷氨酸释放增加和20hz - LTP诱导，而不能挽救受损的NMDAr依赖性LTP。这些发现表明，b通路缺乏可能通过抑制NMDAr依赖性的LTP而损害认知功能，而a通路缺乏可能通过增强突触前谷氨酸释放来促进NMDAr非依赖性的LTP。由于不依赖NMDAr的LTP和增加的突触前谷氨酸释放对L型电压门控Ca2+通道（L‐VGCC）的阻断很敏感，通路缺陷可能影响突触前的L‐VGCC。©2013 Wiley期刊公司
In this study, we used GM2/GD2 synthase knockout (GM2/GD2−/−) mice to examine the influence of deficiency in ganglioside “a‐pathway” and “b‐pathway” on cognitive performances and hippocampal synaptic plasticity. Eight‐week‐old GM2/GD2−/− male mice showed a longer escape‐latency in Morris water maze test and a shorter latency in step‐down inhibitory avoidance task than wild‐type (WT) mice. Schaffer collateral‐CA1 synapses in the hippocampal slices from GM2/GD2−/− mice showed an increase in the slope of EPSPs with reduced paired‐pulse facilitation, indicating an enhancement of their presynaptic glutamate release. In GM2/GD2−/− mice, NMDA receptor (NMDAr)‐dependent LTP could not be induced by high‐frequency (100–200 Hz) tetanus or θ‐burst conditioning stimulation (CS), whereas NMDAr‐independent LTP was induced by medium‐frequency CS (20–50 Hz). The application of mono‐sialoganglioside GM1 in the slice from GM2/GD2−/− mice, to specifically recover the a‐pathway, prevented the increased presynaptic glutamate release and 20 Hz‐LTP induction, whereas it could not rescue the impaired NMDAr‐dependent LTP. These findings suggest that b‐pathway deficiency impairs cognitive function probably through suppression of NMDAr‐dependent LTP, while a‐pathway deficiency may facilitate NMDAr‐independent LTP through enhancing presynaptic glutamate release. As both of the NMDAr‐independent LTP and increased presynaptic glutamate release were sensitive to the blockade of L‐type voltage‐gated Ca2+ channels (L‐VGCC), a‐pathway deficiency may affect presynaptic L‐VGCC. © 2013 Wiley Periodicals, Inc.