Open AccessOridonin Attenuates Synaptic Loss and Cognitive Deficits in an Aβ1–42-Induced Mouse Model of Alzheimer’s Disease
Author(s) -
Sulei Wang,
Liu Yu,
Hui Yang,
Chaosheng Li,
Hui Zhang,
Yun Xu,
Xiaolei Zhu
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0151397
Subject(s) - morris water navigation task , synaptophysin , hippocampus , neuroscience , dendritic spine , synaptic plasticity , synapse , tropomyosin receptor kinase b , creb , in vivo , amyloid beta , cognitive decline , biology , medicine , hippocampal formation , neurotrophic factors , disease , dementia , biochemistry , receptor , immunohistochemistry , microbiology and biotechnology , gene , transcription factor
Synaptic loss induced by beta-amyloid (Aβ) plays a critical role in the pathophysiology of Alzheimer’s disease (AD), but the mechanisms underlying this process remain unknown. In this study, we found that oridonin (Ori) rescued synaptic loss induced by Aβ 1–42 in vivo and in vitro and attenuated the alterations in dendritic structure and spine density observed in the hippocampus of AD mice. In addition, Ori increased the expression of PSD-95 and synaptophysin and promoted mitochondrial activity in the synaptosomes of AD mice. Ori also activated the BDNF/TrkB/CREB signaling pathway in the hippocampus of AD mice. Furthermore, in the Morris water maze test, Ori reduced latency and searching distance and increased the number of platform crosses in AD mice. These data suggest that Ori might prevent synaptic loss and improve behavioral symptoms in Aβ 1–42 -induced AD mice.