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The Journal of Physiological Sciences

, Volume 69, Issue 3, pp 477–488 | Cite as

Xanthoceraside prevented synaptic loss and reversed learning-memory deficits in APP/PS1 transgenic mice

  • Ge Jin
  • Lin Zhu
  • Peng Liu
  • Qian Xu
  • Yue Qi
  • Xiaoyu Zhou
  • Jikai Xu
  • Xuefei Ji
  • Tianyan Chi
  • Libo ZouEmail author
Original Paper
  • 71 Downloads

Abstract

Xanthoceraside, a novel triterpenoid saponin, has been found to attenuate learning and memory impairments in AD animal models. However, whether xanthoceraside has a positive effect on synaptic morphology remains unclear. Herein, we evaluated the effects of xanthoceraside on learning and memory impairments and the abnormalities of synaptic structure in APP/PS1 transgenic mice. The behavioral experiments demonstrated that xanthoceraside attenuated the imaginal memory and spatial learning impairments, and improved social interaction. Transmission electron microscopy and Golgi staining showed that xanthoceraside ameliorated synapse morphology abnormalities and dendritic spine density deficits, respectively. Western-blot analysis identified that xanthoceraside increased the expression of SYP and PSD95, activated BDNF/TrkB/MAPK/ERK and PI3K/Akt signaling pathways, meanwhile decreased the expression of RhoA, ROCK and Snk, increased the levels of SPAR, and activated the BDNF/TrkB/cofilin signaling pathway. Taken together, our study indicated that xanthoceraside improved cognitive function and protected both synaptic morphology and dendritic spine in APP/PS1 transgenic mice, which might be related in part to its activation in the BDNF/TrkB pathway.

Keywords

Xanthoceraside Learning and memory Synaptic structure BDNF TrkB 

Abbreviations

Amyloid-β peptide

NFTs

Intracellular neurofibrillary tangles

BDNF

Brain-derived neurotrophic factor

TrkB

Tropomyosin receptor kinase B

MAPK

Mitogen-activated protein kinases

ERK

Extracellular-signal related kinase

PI3K

Phosphatidylinositol 3 kinase

RhoA

Ras homolog gene A

ROCK2

Rho-associated coiled-coil forming protein kinase 2

Snk

Serum inducible kinase

SPAR

Spine-associated Rap-specific GTPase-activating protein

SYP

Synaptophysin

PSD95

Post-synaptic density protein

Notes

Authors’ contribution

G. Jin and L. Zhu conceived the experiments and contributed to research data; P. Liu, Q. Xu and Y.Q. contributed technical assistance; X. Zou and J. Xu participated in raising animals; and X. Ji and T. Chi revised the manuscript. L. Zou revised the manuscript and supervised the analyses.

Funding

This work was supported by the Research Fund for National Natural Science Foundation (No. 81373992) of China, the Career Development Program for Young Teachers in Shenyang Pharmaceutical University (No. ZQN2015028) and the Doctoral Scientific Research Foundation of Liaoning Province (No. 51120424).

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.

Ethical approval

Animal studies were performed in accordance with the P.R. China legislation on the use and the care of laboratory animals and with the guidelines established by the Institute for Experimental Animals at Shenyang Pharmaceutical University. The protocols were approved by the Committee on the Ethics of Animal Experiments of the Shenyang Pharmaceutical University (SYPU-IACUC-S20140317-04).

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Copyright information

© The Physiological Society of Japan 2019

Authors and Affiliations

  1. 1.Department of Pharmacology, Life Science and Biopharmaceutics SchoolShenyang Pharmaceutical UniversityShenyangPeople’s Republic of China
  2. 2.Shenyang Medical CollegeShenyangPeople’s Republic of China

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