Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Mouse-Prone 8 Mice

Much attention has recently been focused on nutraceuticals, with minimal adverse effects, developed for preventing or treating neurological diseases such as Alzheimer's disease (AD). The present study was conducted to investigate the potential effect on neural development and function of the mi...

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Main Authors: Kazunori Sasaki, Noelia Geribaldi-Doldán, Qingqing Wu, Julie Davies, Francis G. Szele, Hiroko Isoda
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-02-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2020.600575/full
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author Kazunori Sasaki
Kazunori Sasaki
Kazunori Sasaki
Noelia Geribaldi-Doldán
Noelia Geribaldi-Doldán
Qingqing Wu
Qingqing Wu
Julie Davies
Francis G. Szele
Hiroko Isoda
Hiroko Isoda
Hiroko Isoda
author_facet Kazunori Sasaki
Kazunori Sasaki
Kazunori Sasaki
Noelia Geribaldi-Doldán
Noelia Geribaldi-Doldán
Qingqing Wu
Qingqing Wu
Julie Davies
Francis G. Szele
Hiroko Isoda
Hiroko Isoda
Hiroko Isoda
author_sort Kazunori Sasaki
collection DOAJ
description Much attention has recently been focused on nutraceuticals, with minimal adverse effects, developed for preventing or treating neurological diseases such as Alzheimer's disease (AD). The present study was conducted to investigate the potential effect on neural development and function of the microalgae Aurantiochytrium sp. as a nutraceutical. To test neuroprotection by the ethanol extract of Aurantiochytrium (EEA) and a derivative, the n-Hexane layer of EEA (HEEA), amyloid-β-stimulated SH-SY5Y cells, was used as an in vitro AD model. We then assessed the potential enhancement of neurogenesis by EEA and HEEA using murine ex vivo neurospheres. We also administered EEA or HEEA to senescence-accelerated mouse-prone 8 (SAMP8) mice, a non-transgenic strain with accelerated aging and AD-like memory loss for evaluation of spatial learning and memory using the Morris water maze test. Finally, we performed immunohistochemical analysis for assessment of neurogenesis in mice administered EEA. Pretreatment of SH-SY5Y cells with EEA or the squalene-rich fraction of EEA, HEEA, ameliorated amyloid-β-induced cytotoxicity. Interestingly, only EEA-treated cells showed a significant increase in cell metabolism and intracellular adenosine triphosphate production. Moreover, EEA treatment significantly increased the number of neurospheres, whereas HEEA treatment significantly increased the number of β-III-tubulin+ young neurons and GFAP+ astrocytes. SAMP8 mice were given 50 mg/kg EEA or HEEA orally for 30 days. EEA and HEEA decreased escape latency in the Morris water maze in SAMP8 mice, indicating improved memory. To detect stem cells and newborn neurons, we administered BrdU for 9 days and measured BrdU+ cells in the dentate gyrus, a neurogenic stem cell niche of the hippocampus. In SAMP8 mice, EEA rapidly and significantly increased the number of BrdU+GFAP+ stem cells and their progeny, BrdU+NeuN+ mature neurons. In conclusion, our data in aggregate indicate that EEA and its constituents could be developed into a nutraceutical for promoting brain health and function against several age-related diseases, particularly AD.
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spelling doaj.art-6ebab9116f8b4e72b747d787ff24565c2022-12-21T23:34:32ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-02-01810.3389/fcell.2020.600575600575Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Mouse-Prone 8 MiceKazunori Sasaki0Kazunori Sasaki1Kazunori Sasaki2Noelia Geribaldi-Doldán3Noelia Geribaldi-Doldán4Qingqing Wu5Qingqing Wu6Julie Davies7Francis G. Szele8Hiroko Isoda9Hiroko Isoda10Hiroko Isoda11Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, JapanOpen Innovation Laboratory for Food and Medicinal Resource Engineering, National Institute of Advanced Industrial Science and Technology (AIST), University of Tsukuba, Tsukuba, JapanFaculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, JapanAlliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, JapanDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United KingdomAlliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, JapanDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United KingdomDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United KingdomDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United KingdomAlliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, JapanOpen Innovation Laboratory for Food and Medicinal Resource Engineering, National Institute of Advanced Industrial Science and Technology (AIST), University of Tsukuba, Tsukuba, JapanFaculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, JapanMuch attention has recently been focused on nutraceuticals, with minimal adverse effects, developed for preventing or treating neurological diseases such as Alzheimer's disease (AD). The present study was conducted to investigate the potential effect on neural development and function of the microalgae Aurantiochytrium sp. as a nutraceutical. To test neuroprotection by the ethanol extract of Aurantiochytrium (EEA) and a derivative, the n-Hexane layer of EEA (HEEA), amyloid-β-stimulated SH-SY5Y cells, was used as an in vitro AD model. We then assessed the potential enhancement of neurogenesis by EEA and HEEA using murine ex vivo neurospheres. We also administered EEA or HEEA to senescence-accelerated mouse-prone 8 (SAMP8) mice, a non-transgenic strain with accelerated aging and AD-like memory loss for evaluation of spatial learning and memory using the Morris water maze test. Finally, we performed immunohistochemical analysis for assessment of neurogenesis in mice administered EEA. Pretreatment of SH-SY5Y cells with EEA or the squalene-rich fraction of EEA, HEEA, ameliorated amyloid-β-induced cytotoxicity. Interestingly, only EEA-treated cells showed a significant increase in cell metabolism and intracellular adenosine triphosphate production. Moreover, EEA treatment significantly increased the number of neurospheres, whereas HEEA treatment significantly increased the number of β-III-tubulin+ young neurons and GFAP+ astrocytes. SAMP8 mice were given 50 mg/kg EEA or HEEA orally for 30 days. EEA and HEEA decreased escape latency in the Morris water maze in SAMP8 mice, indicating improved memory. To detect stem cells and newborn neurons, we administered BrdU for 9 days and measured BrdU+ cells in the dentate gyrus, a neurogenic stem cell niche of the hippocampus. In SAMP8 mice, EEA rapidly and significantly increased the number of BrdU+GFAP+ stem cells and their progeny, BrdU+NeuN+ mature neurons. In conclusion, our data in aggregate indicate that EEA and its constituents could be developed into a nutraceutical for promoting brain health and function against several age-related diseases, particularly AD.https://www.frontiersin.org/articles/10.3389/fcell.2020.600575/fullAurantiochytrium sp.neuroprotectionadult neurogenesisneuronal stem cellsSAMP8 mice
spellingShingle Kazunori Sasaki
Kazunori Sasaki
Kazunori Sasaki
Noelia Geribaldi-Doldán
Noelia Geribaldi-Doldán
Qingqing Wu
Qingqing Wu
Julie Davies
Francis G. Szele
Hiroko Isoda
Hiroko Isoda
Hiroko Isoda
Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Mouse-Prone 8 Mice
Frontiers in Cell and Developmental Biology
Aurantiochytrium sp.
neuroprotection
adult neurogenesis
neuronal stem cells
SAMP8 mice
title Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Mouse-Prone 8 Mice
title_full Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Mouse-Prone 8 Mice
title_fullStr Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Mouse-Prone 8 Mice
title_full_unstemmed Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Mouse-Prone 8 Mice
title_short Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Mouse-Prone 8 Mice
title_sort microalgae aurantiochytrium sp increases neurogenesis and improves spatial learning and memory in senescence accelerated mouse prone 8 mice
topic Aurantiochytrium sp.
neuroprotection
adult neurogenesis
neuronal stem cells
SAMP8 mice
url https://www.frontiersin.org/articles/10.3389/fcell.2020.600575/full
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