Open AccessL‐3‐n‐butylphthalide Rescues Hippocampal Synaptic Failure and Attenuates Neuropathology in Aged APP / PS 1 Mouse Model of Alzheimer's Disease
Author(s) -
Zhang Yu,
Huang LongJian,
Shi Si,
Xu ShaoFeng,
Wang XiaoLiang,
Peng Ying
Publication year - 2016
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12594
Subject(s) - synaptophysin , dendritic spine , synapse , postsynaptic density , hippocampal formation , synaptic plasticity , neuroscience , microbiology and biotechnology , hippocampus , chemistry , medicine , biology , receptor , immunohistochemistry
Summary Aims 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 / PS 1 AD transgenic mice and related mechanisms. Methods Eighteen‐month‐old APP / PS 1 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, A β plaques, and glial activation were detected by staining. The expressions of synapse‐related proteins were observed by Western blotting. Results 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 PSD 95, synaptophysin ( SYN ), β ‐catenin, and GSK ‐3 β , and attenuated A β plaques and neuroinflammatory responses in aged APP / PS 1 Tg mice. Conclusion L‐ NBP may restore synaptic and spine function in aged APP Tg mice through inhibiting A β plaques deposition and neuroinflammatory response. Wnt/ β ‐catenin signaling pathway may be involved in L‐ NBP ‐related restoration of synaptic function.