Impaired brain development and reduced cognitive function in phospholipase D-deficient mice
Impaired brain development and reduced cognitive function in phospholipase D-deficient mice
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DOI：
10.1016/j.neulet.2014.04.052
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发表时间：
2014-06-20
影响因子：
2.5
通讯作者：
Klein, Jochen
中科院分区：
文献类型：
--
作者：
Burkhardt, Ute;Stegner, David;Klein, Jochen
磷脂酶D（PLD1和PLD2）是信号传导酶，可催化磷脂酰胆碱水解为磷脂酸（一种参与细胞增殖的脂质第二信使）和胆碱（乙酰胆碱（ACh）的前体）。在本研究中，我们研究了PLD1缺失、PLD2缺失或两者均缺失的小鼠的发育和认知功能。我们发现，与野生型小鼠相比，PLD缺失小鼠在产后14 - 27天脑生长减缓。在成年PLD缺失小鼠中，其在社交和物体识别任务中的认知功能受损。通过脑微透析，我们发现野生型小鼠在旷场行为刺激下海马体乙酰胆碱释放量增加4倍，而PLD缺失小鼠释放的乙酰胆碱明显较少。这些结果可能与胎儿酒精综合征和阿尔茨海默病中观察到的认知功能障碍有关。（C）2014爱思唯尔爱尔兰有限公司。保留所有权利。
The phospholipases D (PLD1 and 2) are signaling enzymes that catalyze the hydrolysis of phosphatidylcholine to phosphatidic acid, a lipid second messenger involved in cell proliferation, and choline, a precursor of acetylcholine (ACh). In the present study, we investigated development and cognitive function in mice that were deficient for PLD1, or PLD2, or both. We found that PLD-deficient mice had reduced brain growth at 14-27 days postpartum when compared to wild-type mice. In adult PLO-deficient mice, cognitive function was impaired in social and object recognition tasks. Using brain microdialysis, we found that wild-type mice responded with a 4-fold increase of hippocampal ACh release upon behavioral stimulation in the open field, while PLD-deficient mice released significantly less ACh. These results may be relevant for cognitive dysfunctions observed in fetal alcohol syndrome and in Alzheimer' disease. (C) 2014 Elsevier Ireland Ltd. All rights reserved.