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GLP-1 improves the supportive ability of astrocytes to neurons by promoting aerobic glycolysis in Alzheimer's disease

OBJECTIVE: Astrocytes actively participate in energy metabolism in the brain, and astrocytic aerobic glycolysis disorder is associated with the pathology of Alzheimer's disease (AD). GLP-1 has been shown to improve cognition in AD; however, the mechanism remains unclear. The objectives of this...

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Autores principales: Zheng, Jiaping, Xie, Yunzhen, Ren, Lingjia, Qi, Liqin, Wu, Li, Pan, Xiaodong, Zhou, Jianxing, Chen, Zhou, Liu, Libin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905479/
https://www.ncbi.nlm.nih.gov/pubmed/33556642
http://dx.doi.org/10.1016/j.molmet.2021.101180
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author Zheng, Jiaping
Xie, Yunzhen
Ren, Lingjia
Qi, Liqin
Wu, Li
Pan, Xiaodong
Zhou, Jianxing
Chen, Zhou
Liu, Libin
author_facet Zheng, Jiaping
Xie, Yunzhen
Ren, Lingjia
Qi, Liqin
Wu, Li
Pan, Xiaodong
Zhou, Jianxing
Chen, Zhou
Liu, Libin
author_sort Zheng, Jiaping
collection PubMed
description OBJECTIVE: Astrocytes actively participate in energy metabolism in the brain, and astrocytic aerobic glycolysis disorder is associated with the pathology of Alzheimer's disease (AD). GLP-1 has been shown to improve cognition in AD; however, the mechanism remains unclear. The objectives of this study were to assess GLP-1's glycolytic regulation effects in AD and reveal its neuroprotective mechanisms. METHODS: The Morris water maze test was used to evaluate the effects of liraglutide (an analog of GLP-1) on the cognition of 4-month-old 5 [Formula: see text] FAD mice, and a proteomic analysis and Western blotting were used to assess the proteomic profile changes. We constructed an astrocytic model of AD by treating primary astrocytes with Aβ(1-42). The levels of NAD+ and lactate were examined, and the oxidative levels were assessed by a Seahorse examination. Astrocyte-neuron co-culture was performed to evaluate the effects of GLP-1 on astrocytes’ neuronal support. RESULTS: GLP-1 improved cognition in 4-month-old 5 [Formula: see text] FAD mice by enhancing aerobic glycolysis and reducing oxidative phosphorylation (OXPHOS) levels and oxidative stress in the brain. GLP-1 also alleviated Aβ-induced glycolysis declines in astrocytes, which resulted in reduced OXPHOS levels and reactive oxygen species (ROS) production. The mechanism involved the activation of the PI3K/Akt pathway by GLP-1. Elevation in astrocytic glycolysis improved astrocyte cells’ support of neurons and promoted neuronal survival and axon growth. CONCLUSIONS: Taken together, we revealed GLP-1's capacity to regulate astrocytic glycolysis, providing mechanistic insight into one of its neuroprotective roles in AD and support for the feasibility of energy regulation treatments for AD.
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spelling pubmed-79054792021-03-03 GLP-1 improves the supportive ability of astrocytes to neurons by promoting aerobic glycolysis in Alzheimer's disease Zheng, Jiaping Xie, Yunzhen Ren, Lingjia Qi, Liqin Wu, Li Pan, Xiaodong Zhou, Jianxing Chen, Zhou Liu, Libin Mol Metab Original Article OBJECTIVE: Astrocytes actively participate in energy metabolism in the brain, and astrocytic aerobic glycolysis disorder is associated with the pathology of Alzheimer's disease (AD). GLP-1 has been shown to improve cognition in AD; however, the mechanism remains unclear. The objectives of this study were to assess GLP-1's glycolytic regulation effects in AD and reveal its neuroprotective mechanisms. METHODS: The Morris water maze test was used to evaluate the effects of liraglutide (an analog of GLP-1) on the cognition of 4-month-old 5 [Formula: see text] FAD mice, and a proteomic analysis and Western blotting were used to assess the proteomic profile changes. We constructed an astrocytic model of AD by treating primary astrocytes with Aβ(1-42). The levels of NAD+ and lactate were examined, and the oxidative levels were assessed by a Seahorse examination. Astrocyte-neuron co-culture was performed to evaluate the effects of GLP-1 on astrocytes’ neuronal support. RESULTS: GLP-1 improved cognition in 4-month-old 5 [Formula: see text] FAD mice by enhancing aerobic glycolysis and reducing oxidative phosphorylation (OXPHOS) levels and oxidative stress in the brain. GLP-1 also alleviated Aβ-induced glycolysis declines in astrocytes, which resulted in reduced OXPHOS levels and reactive oxygen species (ROS) production. The mechanism involved the activation of the PI3K/Akt pathway by GLP-1. Elevation in astrocytic glycolysis improved astrocyte cells’ support of neurons and promoted neuronal survival and axon growth. CONCLUSIONS: Taken together, we revealed GLP-1's capacity to regulate astrocytic glycolysis, providing mechanistic insight into one of its neuroprotective roles in AD and support for the feasibility of energy regulation treatments for AD. Elsevier 2021-02-06 /pmc/articles/PMC7905479/ /pubmed/33556642 http://dx.doi.org/10.1016/j.molmet.2021.101180 Text en © 2021 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Zheng, Jiaping
Xie, Yunzhen
Ren, Lingjia
Qi, Liqin
Wu, Li
Pan, Xiaodong
Zhou, Jianxing
Chen, Zhou
Liu, Libin
GLP-1 improves the supportive ability of astrocytes to neurons by promoting aerobic glycolysis in Alzheimer's disease
title GLP-1 improves the supportive ability of astrocytes to neurons by promoting aerobic glycolysis in Alzheimer's disease
title_full GLP-1 improves the supportive ability of astrocytes to neurons by promoting aerobic glycolysis in Alzheimer's disease
title_fullStr GLP-1 improves the supportive ability of astrocytes to neurons by promoting aerobic glycolysis in Alzheimer's disease
title_full_unstemmed GLP-1 improves the supportive ability of astrocytes to neurons by promoting aerobic glycolysis in Alzheimer's disease
title_short GLP-1 improves the supportive ability of astrocytes to neurons by promoting aerobic glycolysis in Alzheimer's disease
title_sort glp-1 improves the supportive ability of astrocytes to neurons by promoting aerobic glycolysis in alzheimer's disease
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905479/
https://www.ncbi.nlm.nih.gov/pubmed/33556642
http://dx.doi.org/10.1016/j.molmet.2021.101180
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