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.

Highlights

  • Increased amyloid-β (Aβ) in the brain is associated with cognitive impairment [1]

  • We investigated whether Spirulina maxima 70% ethanol extract (SM70EE) ameliorated the learning and memory impairments induced by intracerebroventricular (I.C.V.) injection of amyloid-β 1–42 (Aβ1–42) to mice and, if so, whether this effect was mediated through regulating the brain-derived neurotrophic factor (BDNF)/phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and glycogen synthase kinase-3β (GSK-3β) activation

  • SM70EE dose-dependently increased the step-through latency in the Aβ1–42-injected mice

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Summary

Introduction

Increased amyloid-β (Aβ) in the brain is associated with cognitive impairment [1]. These events are proceeded by processing of amyloid precursor protein (APP). The major Aβ peptide generated by γ-secretase cleavage is Aβ1–42 [3], which is more insoluble and neurotoxic [4,5] and has been more strongly associated with cognitive disorders [6] than the other generated peptides. Increased Aβ deposition affects acetylcholine (ACh) and acetylcholinesterase (AChE) [7]. The Aβ1–42-induced reduction of acetylcholine ACh and elevation of AChE is associated with cognitive impairment [9,10]

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