Spirulina maxima Extract Ameliorates Learning and Memory Impairments via Inhibiting GSK-3β Phosphorylation Induced by Intracerebroventricular Injection of Amyloid-β 1-42 in Mice

Int J Mol Sci. 2017 Nov 13;18(11):2401. doi: 10.3390/ijms18112401.

Abstract

Spirulina maxima, a microalga containing high levels of protein and many polyphenols, including chlorophyll a and C-phycocyanin, has antioxidant and anti-inflammatory therapeutic effects. However, the mechanisms where by Spirulina maxima ameliorates cognitive disorders induced by amyloid-β 1-42 (Aβ1-42) are not fully understood. In this study, we investigated whether a 70% ethanol extract of Spirulina maxima (SM70EE) ameliorated cognitive impairments induced by an intracerebroventricular injection of Aβ1-42 in mice. SM70EE increased the step-through latency time in the passive avoidance test and decreased the escape latency time in the Morris water maze test in Aβ1-42-injected mice. SM70EE reduced hippocampal Aβ1-42 levels and inhibited amyloid precursor protein processing-associated factors in Aβ1-42-injected mice. Additionally, acetylcholinesterase activity was suppressed by SM70EE in Aβ1-42-injected mice. Hippocampal glutathione levels were examined to determine the effects of SM70EE on oxidative stress in Aβ1-42-injected mice. SM70EE increased the levels of glutathione and its associated factors that were reduced in Aβ1-42-injected mice. SM70EE also promoted activation of the brain-derived neurotrophic factor/phosphatidylinositol-3 kinase/serine/threonine protein kinase signaling pathway and inhibited glycogen synthase kinase-3β phosphorylation. These findings suggested that SM70EE ameliorated Aβ1-42-induced cognitive impairments by inhibiting the increased phosphorylation of glycogen synthase kinase-3β caused by intracerebroventricular injection of Aβ1-42 in mice.

Keywords: Spirulina maxima 70% ethanol extract (SM70EE); amyloid precursor protein (APP) processing; cognitive impairment; glycogen synthase kinase-3β (GSK-3β); oxidative stress.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Amyloid beta-Peptides / administration & dosage
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Glutathione / metabolism
  • Glycogen Synthase Kinase 3 beta / metabolism*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Injections, Intraventricular
  • Male
  • Maze Learning*
  • Memory Disorders / drug therapy*
  • Memory Disorders / etiology
  • Mice
  • Mice, Inbred ICR
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / toxicity
  • Phosphorylation
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Protein Processing, Post-Translational
  • Spirulina / chemistry*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Plant Extracts
  • amyloid beta-protein (1-42)
  • Glycogen Synthase Kinase 3 beta
  • Acetylcholinesterase
  • Glutathione