Soybean isoflavone ameliorates β-amyloid 1-42-induced learning and memory deficit in rats by protecting synaptic structure and function

Synapse. 2013 Dec;67(12):856-64. doi: 10.1002/syn.21692. Epub 2013 Jul 4.

Abstract

This research aims to investigate whether soybean isoflavone (SIF) could alleviate the learning and memory deficit induced by β-amyloid peptides 1-42 (Aβ 1-42) by protecting the synapses of rats. Adult male Wistar rats were randomly allocated to the following groups: (1) control group; (2) Aβ 1-42 group; (3) SIF group; (4) SIF + Aβ 1-42 group (SIF pretreatment group) according to body weight. The 80 mg/kg/day of SIF was administered orally by gavage to the rats in SIF and SIF+Aβ 1-42 groups. Aβ 1-42 was injected into the lateral cerebral ventricle of rats in Aβ 1-42 and SIF+Aβ 1-42 groups. The ability of learning and memory, ultramicrostructure of hippocampal synapses, and expression of synaptic related proteins were investigated. The Morris water maze results showed the escape latency and total distance were decreased in the rats of SIF pretreatment group compared to the rats in Aβ1-42 group. Furthermore, SIF pretreatment could alleviate the synaptic structural damage and antagonize the down-regulation expressions of below proteins induced by Aβ1-42: (1) mRNA and protein of the synaptophysin and postsynaptic density protein 95 (PSD-95); (2) protein of calmodulin (CaM), Ca(2+) /calmodulin-dependent protein kinase II (CaMK II), and cAMP response element binding protein (CREB); (3) phosphorylation levels of CaMK II and CREB (pCAMK II, pCREB). These results suggested that SIF pretreatment could ameliorate the impairment of learning and memory ability in rats induced by Aβ 1-42, and its mechanism might be associated with the protection of synaptic plasticity by improving the synaptic structure and regulating the synaptic related proteins.

Keywords: Aβ; learning and memory; neuroprotection; soybean isoflavone; synaptic dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Calmodulin / genetics
  • Calmodulin / metabolism
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Disks Large Homolog 4 Protein
  • Glycine max / chemistry*
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / physiology
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Isoflavones / pharmacology*
  • Isoflavones / therapeutic use
  • Male
  • Maze Learning / drug effects*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Memory / drug effects*
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy
  • Peptide Fragments / toxicity*
  • Phosphorylation
  • Phytotherapy
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Rats
  • Rats, Wistar
  • Reaction Time
  • Synapses / drug effects*
  • Synapses / metabolism
  • Synapses / physiology
  • Synapses / ultrastructure
  • Transcription, Genetic

Substances

  • Amyloid beta-Peptides
  • Calmodulin
  • Cyclic AMP Response Element-Binding Protein
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Isoflavones
  • Membrane Proteins
  • Peptide Fragments
  • Plant Extracts
  • amyloid beta-protein (1-42)
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2