Xian Xunde, Liu Tingting, Yu Jia, Wang Yuhui, Miao Yifei, Zhang Jianjun, Yu Yan, Ross Colin, Karasinska Joanna M, Hayden Michael R, Liu George, Chui Dehua
Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, 38 Xueyuan Road, Hai Dian District, Beijing, China.
J Neurosci. 2009 Apr 8;29(14):4681-5. doi: 10.1523/JNEUROSCI.0297-09.2009.
Lipoprotein lipase (LPL) is predominantly expressed in adipose and muscle where it plays a crucial role in the metabolism of triglyceride-rich plasma lipoproteins. LPL is also expressed in the brain with highest levels found in the pyramidal cells of the hippocampus, suggesting a possible role for LPL in the regulation of cognitive function. However, very little is currently known about the specific role of LPL in the brain. We have generated a mouse model of LPL deficiency which was rescued from neonatal lethality by somatic gene transfer. These mice show no exogenous and endogenous LPL expression in the brain. To study the role of LPL in learning and memory, the performance of LPL-deficient mice was tested in two cognitive tests. In a water maze test, LPL-deficient mice exhibited increased latency to escape platform and increased mistake frequency. Decreased latency to platform in the step-down inhibitory avoidance test was observed, consistent with impaired learning and memory in these mice. Transmission electron microscopy revealed a significant decrease in the number of presynaptic vesicles in the hippocampus of LPL-deficient mice. The levels of the presynaptic marker synaptophysin were also reduced in the hippocampus, whereas postsynaptic marker postsynaptic density protein 95 levels remained unchanged in LPL-deficient mice. Theses findings indicate that LPL plays an important role in learning and memory function possibly by influencing presynaptic function.
脂蛋白脂肪酶（LPL）主要在脂肪组织和肌肉中表达，在富含甘油三酯的血浆脂蛋白代谢中起关键作用。LPL在大脑中也有表达，在海马体的锥体细胞中含量最高，这表明LPL可能在认知功能调节中发挥作用。然而，目前对于LPL在大脑中的具体作用知之甚少。我们构建了一种LPL缺陷的小鼠模型，通过体细胞基因转移使其从新生儿致死中获救。这些小鼠大脑中没有外源性和内源性LPL表达。为了研究LPL在学习和记忆中的作用，在两项认知测试中对LPL缺陷小鼠的行为表现进行了测试。在水迷宫测试中，LPL缺陷小鼠逃避平台的潜伏期延长，错误频率增加。在递减式抑制回避测试中，观察到小鼠到达平台的潜伏期缩短，这与这些小鼠学习和记忆受损一致。透射电子显微镜显示，LPL缺陷小鼠海马体中突触前囊泡数量显著减少。海马体中突触前标记物突触素的水平也降低，而LPL缺陷小鼠中突触后标记物突触后致密蛋白95的水平保持不变。这些发现表明，LPL可能通过影响突触前功能在学习和记忆功能中发挥重要作用。
