IMPAIRED SYNAPTIC VESICLE RECYCLING CONTRIBUTES TO PRESYNAPTIC DYSFUNCTION IN LIPOPROTEIN LIPASE-DEFICIENT MICE
IMPAIRED SYNAPTIC VESICLE RECYCLING CONTRIBUTES TO PRESYNAPTIC DYSFUNCTION IN LIPOPROTEIN LIPASE-DEFICIENT MICE
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突触小泡回收受损导致脂蛋白脂肪酶缺陷小鼠的突触前功能障碍
DOI：
10.1016/j.neuroscience.2014.07.080
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发表时间：
2014-11-07
期刊：
影响因子：
3.3
通讯作者：
Chui, D.
中科院分区：
文献类型：
--
作者：
Liu, X.;Zhang, B.;Chui, D.
脂蛋白脂酶（LPL）在海马神经元中高水平表达，但其功能尚不清楚。我们以前报道过，LPL缺陷的小鼠有学习和记忆障碍，海马神经元中的突触囊泡较少，但LPL缺陷的神经元中的突触活动的性质仍然没有探索。在这项研究中，我们发现在LPL缺陷的神经元中，微型兴奋性突触后电流（mEPSC）的频率和易释放池（RRP）的大小减少，这导致突触前功能障碍和可塑性损伤，而不改变突触后活动。我们证明，突触囊泡回收，这是已知的发挥重要作用，在保持活跃的突触RRP的大小，LPL缺陷的神经元受损。此外，脂质检测显示缺乏二十二碳六烯酸（DHA）和花生四烯酸（AA）在LPL缺陷小鼠的海马;外源性DHA或AA补充部分恢复突触囊泡再循环能力。这些结果表明，受损的突触囊泡回收的结果缺乏DHA和AA，并有助于突触前功能障碍和可塑性损伤LPL缺乏的神经元。(C)2014年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Lipoprotein lipase (LPL) is expressed at high levels in hippocampal neurons, although its function is unclear. We previously reported that LPL-deficient mice have learning and memory impairment and fewer synaptic vesicles in hippocampal neurons, but properties of synaptic activity in LPL-deficient neurons remain unexplored. In this study, we found reduced frequency of miniature excitatory postsynaptic currents (mEPSCs) and readily releasable pool (RRP) size in LPL-deficient neurons, which led to presynaptic dysfunction and plasticity impairment without altering postsynaptic activity. We demonstrated that synaptic vesicle recycling, which is known to play an important role in maintaining the RRP size in active synapses, is impaired in LPL-deficient neurons. Moreover, lipid assay revealed deficient docosahexaenoic acid (DHA) and arachidonic acid (AA) in the hippocampus of LPL-deficient mice; exogenous DHA or AA supplement partially restored synaptic vesicle recycling capability. These results suggest that impaired synaptic vesicle recycling results from deficient DHA and AA and contributes to the presynaptic dysfunction and plasticity impairment in LPL-deficient neurons. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.