Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783655119592620032 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7905479 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhengjiaping glp1improvesthesupportiveabilityofastrocytestoneuronsbypromotingaerobicglycolysisinalzheimersdisease AT xieyunzhen glp1improvesthesupportiveabilityofastrocytestoneuronsbypromotingaerobicglycolysisinalzheimersdisease AT renlingjia glp1improvesthesupportiveabilityofastrocytestoneuronsbypromotingaerobicglycolysisinalzheimersdisease AT qiliqin glp1improvesthesupportiveabilityofastrocytestoneuronsbypromotingaerobicglycolysisinalzheimersdisease AT wuli glp1improvesthesupportiveabilityofastrocytestoneuronsbypromotingaerobicglycolysisinalzheimersdisease AT panxiaodong glp1improvesthesupportiveabilityofastrocytestoneuronsbypromotingaerobicglycolysisinalzheimersdisease AT zhoujianxing glp1improvesthesupportiveabilityofastrocytestoneuronsbypromotingaerobicglycolysisinalzheimersdisease AT chenzhou glp1improvesthesupportiveabilityofastrocytestoneuronsbypromotingaerobicglycolysisinalzheimersdisease AT liulibin glp1improvesthesupportiveabilityofastrocytestoneuronsbypromotingaerobicglycolysisinalzheimersdisease |