The protective mechanism underlying phenylethanoid glycosides (PHG) actions on synaptic plasticity in rat Alzheimer's disease model induced by beta amyloid 1-42

J Toxicol Environ Health A. 2018;81(21):1098-1107. doi: 10.1080/15287394.2018.1501861. Epub 2018 Nov 15.

Abstract

Phenylethanoid glycosides (PHG), derived from Herba cistanche, were found to exert protective effects on cognitive dysfunctions by improving synaptic plasticity in Alzheimer's disease (AD) rat model. However, the mechanisms underlying these effects of PHG on synaptic plasticity remain to be determined. Thus the aim of this study was to examine the influence of PHG on synaptic plasticity in male AD rat model induced by bilateral central nervous system ventricle injections of beta amyloid 1-42 oligomers (Aβ1-42). The following parameters were measured: (1) number of intact pyramidal cells in hippocampal CA1 region by Nissl staining, (2) post synaptic density 95 (PSD-95), phosphorylated N-methyl-D-aspartate receptor-1(p-NMDAR1) and (3) phosphorylated Tau protein (p-Tau) by immunohistochemistry and western blot. In addition, the content of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined. Aβ1-42 lowered the number of intact pyramidal cells in hippocampal CA1 region. In contrast, treatment with PHG significantly elevated this cell number. Aβ1-42 significantly diminished protein expression levels of PSD-95 accompanied by elevated protein expression levels of p-NMDAR1 and p-Tau. PHG markedly increased protein expression levels of PSD-95, but significantly reduced protein expression levels of p-NMDAR1 and p-Tau. Further, Aβ1-42 markedly increased MDA content concomitantly with reduced activities of SOD and GSH-Px. PHG significantly decreased MDA content accompanied by elevated activities of SOD and GSH-Px. Data suggest that the protective effects of PHG on synaptic plasticity may involve inhibition of cytotoxicity-mediated by Aβ-1-42 administration and reduction of oxidant stress.

Keywords: Alzheimer’s disease; Tau protein; free radicals; phenylethanoid glycosides; synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / prevention & control*
  • Amyloid beta-Peptides / pharmacology
  • Animals
  • CA1 Region, Hippocampal / drug effects
  • Cistanche / chemistry*
  • Cognitive Dysfunction / prevention & control*
  • Glycosides / pharmacology*
  • Infusions, Intraventricular
  • Male
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuronal Plasticity / drug effects*
  • Phosphorylation
  • Post-Synaptic Density / drug effects
  • Protective Agents / pharmacology*
  • Pyramidal Cells / drug effects
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • tau Proteins / genetics
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • GRIN1 protein, human
  • Glycosides
  • MAPT protein, human
  • Nerve Tissue Proteins
  • Protective Agents
  • Receptors, N-Methyl-D-Aspartate
  • tau Proteins