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

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.

Spirulina Enhances Bone Modeling in Growing Male Rats by Regulating Growth-Related Hormones

“…The antioxidant compounds in spirulina, such as phycobilins and phycocyanins, also inhibit the activities of catalytic enzymes, such as lipoxygenase and cyclooxygenase, or enhance the activity of enzymes, such as glutathione peroxidase, catalase, and superoxide dismutase [59,60]. These polyphenols were reported to have anti-inflammatory, antiviral, antioxidant, antithrombotic, vasodilatory, antidiabetic, neuroprotective, hepatoprotective, and anticarcinogenic properties [21,22,24,28,29,32,[35][36][37][59][60][61][62][63]. However, the metabolic pathways for the formation of phenolic compounds in spirulina and their importance are still unknown [64].…”

Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases

“…ese findings indicated that Spirulina maxima extract ameliorated cognitive impairment through the inhibition of Aβ accumulation and acetylcholinesterase activity. Spirulina maxima extract also suppressed hippocampal oxidative stress of Aβ (1-42)-induced mice through enhancing the antioxidant system in the glutathione metabolism pathway by increasing the GSH level and attenuating the decrease of glutathione peroxidase and glutathione reductase protein expression levels [227]. is suggested that the inhibition of Aβ accumulation and acetylcholinesterase activity by Spirulina maxima extract could contribute to the suppression of oxidative stress.…”

“…Another cyanobacterium, Spirulina maxima, belonging to the Oscillatoriaceae family, has been known to have many physiologically active substances such as carotenoids, chlorophylls, polysaccharides, vitamins, and C-phycocyanin [225,226]. In mouse model of Alzheimer's disease induced by Aβ , Spirulina maxima extract ameliorated learning and memory impairments in Aβ (1-42)-induced mice (assessed using the passive avoidance and Morris water maze tests), decreased the protein expression levels of hippocampal Aβ (1-42), amyloid precursor protein (APP), and β-site APP cleaving enzyme 1 (BACE1) and attenuated the increase in acetylcholinesterase activity in the hippocampal oxidative stress of Aβ (1-42)-induced mice [227]. ese findings indicated that Spirulina maxima extract ameliorated cognitive impairment through the inhibition of Aβ accumulation and acetylcholinesterase activity.…”

“…is suggested that the inhibition of Aβ accumulation and acetylcholinesterase activity by Spirulina maxima extract could contribute to the suppression of oxidative stress. Moreover, Spirulina maxima extract increased the BDNF level, upregulated the phosphorylated PI3K and the phosphorylated Akt, and suppressed the phosphorylated glycogen synthase kinase-3β (GSK3β) in the hippocampal oxidative stress of Aβ (1-42)-induced mice [227].…”

Mineralocorticoid receptor antagonist‐mediated cognitive improvement in a mouse model of Alzheimer's type: possible involvement of BDNF‐H2S‐Nrf2 signaling

“…Amyloid‐β (Aβ) is considered as one of the major pathological mediators in the pathogenesis of Alzheimer's disease (AD) and abnormal accumulation of Aβ impair synaptic function and induces cognitive deficits. The development of cognitive deficits of Alzheimer's type in animals is very successfully done by an intracerebroventricular injection (ICV) of Aβ 1‐42, which delivers the peptide in the ventricles of the brain [24,25]. Accordingly, a single ICV injection of Aβ 1‐42 (100 µ m /10 µL) was employed to induce symptoms of Alzheimer's disease in mice as per previously reported studies [26].…”