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Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits
Published on: March 16, 2016
Spirulina maxima Extract Ameliorates Learning and Memory Impairments via Inhibiting GSK-3β Phosphorylation Induced by
Eun-Jeong Koh1, Kui-Jin Kim2, Ji-Hyeon Song3
1Department of Food Science and Biotechnology, College of Life Science, CHA University, Seongnam, Kyonggi 13488, Korea. kej763@naver.com.
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.
Insights
Spirulina maxima extract (SM70EE) improved memory and reduced amyloid-beta plaques in mice. This natural compound combats cognitive decline by reducing oxidative stress and inhibiting key harmful proteins.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Spirulina maxima is a microalga rich in proteins and polyphenols with known antioxidant and anti-inflammatory properties.
- Amyloid-beta 1-42 (Aβ1-42) induced cognitive disorders are a significant challenge, and their underlying mechanisms require further elucidation.
- The therapeutic potential of Spirulina maxima in mitigating Aβ1-42 related cognitive impairments is not fully understood.
Purpose of the Study:
- To investigate the effects of a 70% ethanol extract of Spirulina maxima (SM70EE) on cognitive impairments induced by Aβ1-42 in a mouse model.
- To explore the underlying mechanisms by which SM70EE ameliorates Aβ1-42-induced cognitive deficits.
Main Methods:
- Aβ1-42 was administered via intracerebroventricular injection in mice to induce cognitive impairment.
- Behavioral tests, including the passive avoidance and Morris water maze tests, were used to assess cognitive function.
- Levels of hippocampal Aβ1-42, amyloid precursor protein processing factors, acetylcholinesterase activity, and glutathione were measured.
- The activation of the brain-derived neurotrophic factor (BDNF)/phosphatidylinositol-3 kinase (PI3K)/serine/threonine protein kinase (Akt) signaling pathway and glycogen synthase kinase-3β (GSK-3β) phosphorylation were analyzed.
Main Results:
- SM70EE significantly improved cognitive performance in Aβ1-42 injected mice, evidenced by increased step-through latency and decreased escape latency.
- SM70EE treatment reduced hippocampal Aβ1-42 levels, inhibited amyloid precursor protein processing, and suppressed acetylcholinesterase activity.
- SM70EE increased hippocampal glutathione levels and associated factors, indicating a reduction in oxidative stress.
- SM70EE promoted the activation of the BDNF/PI3K/Akt pathway and inhibited GSK-3β phosphorylation.
Conclusions:
- SM70EE effectively ameliorates Aβ1-42-induced cognitive impairments in mice.
- The protective effects of SM70EE are mediated through the inhibition of GSK-3β phosphorylation, reduction of oxidative stress, and modulation of key signaling pathways.
- Spirulina maxima extract shows promise as a therapeutic agent for cognitive disorders associated with amyloid pathology.
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