title: L-3-n-butylphthalide Rescues Hippocampal Synaptic Failure and Attenuates Neuropathology in Aged APP/PS1 Mouse Model of Alzheimer's Disease.
abstract: Our previous studies showed that L-3-n-butylphthalide (L-NBP), an extract from seeds of Apium graveolens Linn (Chinese celery), improved cognitive ability in animal models of cerebral ischemia, vascular dementia, and Alzheimer's disease (AD). It is well known that cognitive deficit of AD is caused by synaptic dysfunction. In this study, we investigated the effect of L-NBP on hippocampal synaptic function in APP/PS1 AD transgenic mice and related mechanisms.
  
  
  
  Eighteen-month-old APP/PS1 transgenic (Tg) mice were administrated 15 mg/kg L-NBP by oral gavage for 3 months. Synaptic morphology and the thickness of postsynaptic density (PSD) in hippocampal neurons were investigated by electron microscope. The dendritic spines, Aβ plaques, and glial activation were detected by staining. The expressions of synapse-related proteins were observed by Western blotting.
  
  
  
  L-NBP treatment significantly increased the number of synapses and apical dendritic thorns and the thickness of PSD, increased the expression levels of synapse-associated proteins including PSD95, synaptophysin (SYN), β-catenin, and GSK-3β, and attenuated Aβ plaques and neuroinflammatory responses in aged APP/PS1 Tg mice.
  
  
  
  L-NBP may restore synaptic and spine function in aged APP Tg mice through inhibiting Aβ plaques deposition and neuroinflammatory response. Wnt/β-catenin signaling pathway may be involved in L-NBP-related restoration of synaptic function.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Long-Jian
authors.initials: LJ
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Si
authors.initials: S
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Shao-Feng
authors.initials: SF
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D053764:Presenilin-1 / Q000235:genetics; D013569:Synapses / Q000187:drug effects* / Q000648:ultrastructure; D051176:beta Catenin / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D001572:Benzofurans; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018696:Neuroprotective Agents; C508853:PSEN1 protein, human; D053764:Presenilin-1; D051176:beta Catenin; C027125:3-n-butylphthalide; D000071679:Glycogen Synthase Kinase 3 beta
keywords: Aβ; Golgi staining; L-3-n-butylphthalide; Mitochondrial function; Synaptic plasticity