title: Impaired synaptic vesicle recycling contributes to presynaptic dysfunction in lipoprotein lipase-deficient mice.
abstract: 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.
authors.affiliation: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: B
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.affiliation: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: A
authors.initials: A
authors.lastname: Huang
authors.affiliation: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.affiliation: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: X
authors.initials: X
authors.lastname: Tian
authors.affiliation: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tong
authors.affiliation: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: T
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: T
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: G
authors.initials: G
authors.lastname: Xing
authors.affiliation: Peking University Third Hospital, Beijing 100191, China.
authors.forename: W
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Peking University Third Hospital, Beijing 100191, China.
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.affiliation: Peking University Third Hospital, Beijing 100191, China.
authors.forename: D
authors.initials: D
authors.lastname: Fan
authors.affiliation: Diabetes and Obesity Research Center, Sanford/Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: X
authors.initials: X
authors.lastname: Han
authors.affiliation: Institute of Cardiovascular Science, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: G
authors.initials: G
authors.lastname: Liu
authors.affiliation: Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing 100191, China; School of Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: dchui@bjmu.edu.cn.
authors.forename: D
authors.initials: D
authors.lastname: Chui
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008401:Gas Chromatography-Mass Spectrometry; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D008072:Hyperlipoproteinemia Type I / Q000188:drug therapy / Q000503:physiopathology; D008071:Lipoprotein Lipase / Q000172:deficiency* / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000201:enzymology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000503:physiopathology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000201:enzymology*; D046509:Tissue Culture Techniques
chemical_list: D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D008071:Lipoprotein Lipase
keywords: lipoprotein lipase; presynaptic dysfunction; readily releasable pool (RRP); synaptic plasticity; synaptic vesicle recycling