Astaxanthin supplementation enhances adult hippocampal neurogenesis and spatial memory in mice

Yook, Jang Soo; Okamoto, Masahiro; Rakwal, Randeep; Shibato, Junko; Lee, Min Chul; Matsui, Takashi; Chang, Hyuk Ki; Cho, Joon Yong; Soya, Hideaki

doi:10.1002/mnfr.201500634

Cited by 38 publications

(30 citation statements)

References 47 publications

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“…Other studies also reported that administration of astaxanthin [80 mg/kg/day, oral gavage for 10 weeks (Yang et al, 2019); 25 mg/kg/day, oral gavage for 10 weeks (4 day/week) (Zhou et al, 2015)] did not affect spatial learning and memory in a Morris water maze test in WT mice. However, a higher dose of astaxanthin (0.5% astaxanthin-containing diet) for 8 weeks enhanced neurogenesis and improved special memory in male WT C57BL/6J mice (Yook et al, 2016). These findings suggest that feeding of normal chow with 0.02% astaxanthin might not affect spatial learning and memory in a Barnes maze test in WT mice although normal chow with astaxanthin in doses higher than 0.02% might enhance learning and memory even in WT mice.…”

Section: Protective Mechanisms Of Astaxanthinmentioning

confidence: 84%

“…In the present study, the WT mice were fed only normal chow without 0.02% astaxanthin, but not normal chow with 0.02% astaxanthin. A previous study reported that feeding of 0.02% astaxanthin-containing diet for 8 weeks did not affect adult hippocampal neurogenesis in male WT C57BL/6J mice (Yook et al, 2016). Other studies also reported that administration of astaxanthin [80 mg/kg/day, oral gavage for 10 weeks (Yang et al, 2019); 25 mg/kg/day, oral gavage for 10 weeks (4 day/week) (Zhou et al, 2015)] did not affect spatial learning and memory in a Morris water maze test in WT mice.…”

Section: Protective Mechanisms Of Astaxanthinmentioning

confidence: 92%

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Astaxanthin Ameliorated Parvalbumin-Positive Neuron Deficits and Alzheimer’s Disease-Related Pathological Progression in the Hippocampus of AppNL-G-F/NL-G-F Mice

et al. 2020

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Growing evidence suggests that oxidative stress due to amyloid b (Ab) accumulation is involved in Alzheimer's disease (AD) through the formation of amyloid plaque, which leads to hyperphosphorylation of tau, microglial activation, and cognitive deficits. The dysfunction or phenotypic loss of parvalbumin (PV)-positive neurons has been implicated in cognitive deficits. Astaxanthin is one of carotenoids and known as a highly potent antioxidant. We hypothesized that astaxanthin's antioxidant effects may prevent the onset of cognitive deficits in AD by preventing AD pathological processes associated with oxidative stress. In the present study, we investigated the effects of astaxanthin intake on the cognitive and pathological progression of AD in a mouse model of AD. The App NL-G-F/NL-G-F mice were fed with or without astaxanthin from 5-to-6 weeks old, and cognitive functions were evaluated using a Barnes maze test at 6 months old. PV-positive neurons were investigated in the hippocampus. Ab42 deposits, accumulation of microglia, and phosphorylated tau (pTau) were immunohistochemically analyzed in the hippocampus. The hippocampal anti-oxidant status was also investigated. The Barnes maze test indicated that astaxanthin significantly ameliorated memory deficits. Astaxanthin reduced Ab42 deposition and pTau-positive areal fraction, while it increased PVpositive neuron density and microglial accumulation per unit fraction of Ab42 deposition in the hippocampus. Furthermore, astaxanthin increased total glutathione (GSH) levels, although 4-hydroxy-2,3-trans-nonenal (4-HNE) protein adduct levels (oxidative stress marker) remained high in the astaxanthin supplemented mice. The results indicated that astaxanthin ameliorated memory deficits and significantly reversed AD pathological processes (Ab42 deposition, pTau formation, GSH decrease, and PV-positive neuronal

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Section: Protective Mechanisms Of Astaxanthinmentioning

confidence: 84%

Section: Protective Mechanisms Of Astaxanthinmentioning

confidence: 92%

Astaxanthin Ameliorated Parvalbumin-Positive Neuron Deficits and Alzheimer’s Disease-Related Pathological Progression in the Hippocampus of AppNL-G-F/NL-G-F Mice

et al. 2020

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“…The mice from the exercise groups ran following the appropriate running protocol (four weeks) below their VT (SI Appendix, Table S7). The mice received a nonpurified basal diet with either AX or a placebo (AstaReal powder 20F; AstaReal Co. Ltd) at concentrations of 0.5% (SI Appendix, Table S8) (32).…”

Section: Methodsmentioning

confidence: 99%

“…Among potential dietary supplements, we focused on astaxanthin (AX), a red carotenoid with various health benefits, including enhancement of cognition. AX has highly antioxidant and antiinflammatory properties, with reportedly strong neuroprotective effects (31), and it enhances AHN and spatial memory (32), suggesting that it also has beneficial effects equivalent to those of ME on hippocampal functions. Hence, we hypothesized that ME-enhanced hippocampal neurogenesis and memory might be further improved with dietary AX via mediation by a neurotrophic factor such as h-LEP.…”

mentioning

confidence: 99%

Leptin in hippocampus mediates benefits of mild exercise by an antioxidant on neurogenesis and memory

Yook

Rakwal

Shibato

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Regular exercise and dietary supplements with antioxidants each have the potential to improve cognitive function and attenuate cognitive decline, and, in some cases, they enhance each other. Our current results reveal that low-intensity exercise (mild exercise, ME) and the natural antioxidant carotenoid astaxanthin (AX) each have equivalent beneficial effects on hippocampal neurogenesis and memory function. We found that the enhancement by ME combined with AX in potentiating hippocampus-based plasticity and cognition is mediated by leptin (LEP) made and acting in the hippocampus. In assessing the combined effects upon wild-type (WT) mice undergoing ME with or without an AX diet for four weeks, we found that, when administrated alone, ME and AX separately enhanced neurogenesis and spatial memory, and when combined they were at least additive in their effects. DNA microarray and bioinformatics analyses revealed not only the up-regulation of an antioxidant gene, ABHD3, but also that the up-regulation of LEP gene expression in the hippocampus of WT mice with ME alone is further enhanced by AX. Together, they also increased hippocampal LEP (h-LEP) protein levels and enhanced spatial memory mediated through AKT/STAT3 signaling. AX treatment also has direct action on human neuroblastoma cell lines to increase cell viability associated with increased LEP expression. In LEP-deficient mice (ob/ob), chronic infusion of LEP into the lateral ventricles restored the synergy. Collectively, our findings suggest that not only h-LEP but also exogenous LEP mediates effects of ME on neural functions underlying memory, which is further enhanced by the antioxidant AX.hippocampal leptin | mild exercise | astaxanthin | antioxidant | spatial memory P ositive lifestyle changes including physical activity and diet are believed to be beneficial for promoting brain health and slowing cognitive decline of Alzheimer's disease (AD). Exercise is an important factor in improving hippocampus-related cognition by enhancing adult hippocampal neurogenesis (AHN) in rodents (1). Although dietary supplements such as docosahexaenoic acid (DHA) and epicatechin (EGCG) have been shown to potentiate the effects of voluntary exercise on memory function (2-4), voluntary exercise alone, not in combination with EGCG, improves AHN and memory functions (5, 6). However, previous animal studies were limited in their applicability to clinical trials because of the uncertainty concerning exercise intensity. To translate our mild exercise (ME) animal model to humans, we developed a quantitative evaluation system based on lactate threshold (LT) and showed that ME has beneficial effects on AHN and spatial memory in animals (7, 8) and on hippocampal memory function in young humans (9). This raises the question of whether, for translation to humans, a combined intervention of dietary supplements and ME could enhance memory function and neuronal plasticity.While mechanisms of exercise-enhanced hippocampal function are not fully understood, several molecular factors includin...

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“…Recent studies [4,101] have reported on the direct relationship between the healthy effects of astaxanthin on human brain and promotion of neurogenesis and plasticity, two processes that significantly decrease with age [29] and lead to cognitive decline among elderly people. Although the molecular process has not been completely elucidated, astaxanthin promotes neurogenesis and improves behavioral performance in hippocampal-dependent tasks; this could represent the predominant mechanism induced by astaxanthin, acting on cognitive functions and neurodegeneration caused by AD [4].…”

Section: Astaxanthin Against Alzheimer Disease (Ad)mentioning

confidence: 99%

On the Neuroprotective Role of Astaxanthin: New Perspectives?

et al. 2018

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Astaxanthin is a carotenoid with powerful antioxidant and anti-inflammatory activity produced by several freshwater and marine microorganisms, including bacteria, yeast, fungi, and microalgae. Due to its deep red-orange color it confers a reddish hue to the flesh of salmon, shrimps, lobsters, and crayfish that feed on astaxanthin-producing organisms, which helps protect their immune system and increase their fertility. From the nutritional point of view, astaxanthin is considered one of the strongest antioxidants in nature, due to its high scavenging potential of free radicals in the human body. Recently, astaxanthin is also receiving attention for its effect on the prevention or co-treatment of neurological pathologies, including Alzheimer and Parkinson diseases. In this review, we focus on the neuroprotective properties of astaxanthin and explore the underlying mechanisms to counteract neurological diseases, mainly based on its capability to cross the blood-brain barrier and its oxidative, anti-inflammatory, and anti-apoptotic properties.

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Astaxanthin supplementation enhances adult hippocampal neurogenesis and spatial memory in mice

Abstract: ASX supplementation enhanced AHN and spatial memory, and a DNA microarray approach provided, for the first time, novel molecular insights into ASX action.

Cited by 38 publications

References 47 publications

Astaxanthin Ameliorated Parvalbumin-Positive Neuron Deficits and Alzheimer’s Disease-Related Pathological Progression in the Hippocampus of AppNL-G-F/NL-G-F Mice

Astaxanthin Ameliorated Parvalbumin-Positive Neuron Deficits and Alzheimer’s Disease-Related Pathological Progression in the Hippocampus of AppNL-G-F/NL-G-F Mice

Leptin in hippocampus mediates benefits of mild exercise by an antioxidant on neurogenesis and memory

On the Neuroprotective Role of Astaxanthin: New Perspectives?

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