Oridonin Attenuates Synaptic Loss and Cognitive Deficits in an Aβ1-42-Induced Mouse Model of Alzheimer's Disease

PLoS One. 2016 Mar 14;11(3):e0151397. doi: 10.1371/journal.pone.0151397. eCollection 2016.

Abstract

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 Aβ1-42 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 Aβ1-42-induced AD mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / pathology*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Dendritic Spines / drug effects
  • Dendritic Spines / metabolism
  • Dendritic Spines / pathology
  • Disks Large Homolog 4 Protein
  • Diterpenes, Kaurane / pharmacology
  • Diterpenes, Kaurane / therapeutic use*
  • Guanylate Kinases / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Male
  • Membrane Proteins / metabolism
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Receptor, trkB / metabolism
  • Signal Transduction / drug effects
  • Synapses / drug effects
  • Synapses / metabolism*
  • Synaptophysin / metabolism

Substances

  • Amyloid beta-Peptides
  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Disks Large Homolog 4 Protein
  • Diterpenes, Kaurane
  • Dlg4 protein, mouse
  • Membrane Proteins
  • Synaptophysin
  • oridonin
  • Receptor, trkB
  • Guanylate Kinases

Grants and funding

This work was supported by National Nature Science Foundation of China (No. 81200839, No. 81230026, and No. 81171085) and Nanjing Medical Technology Development Project (No. YKK13086). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.