Correction: Metabolic changes and inflammation in cultured astrocytes from the 5xFAD mouse model of Alzheimer's disease: Alleviation by pantethine

Gijsel-Bonnello, Manuel van; Baranger, Kévin; Benech, Philippe; Rivera, Santiago; Khrestchatisky, Michel; Reggi, Max de; Gharib, Bouchra

doi:10.1371/journal.pone.0194586

Cited by 20 publications

(3 citation statements)

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“…Lactate generated from astrocytic glycolysis is a vital alternative fuel for neurons when faced with energy challenges, and glycolytic enhancement was found to be promising in NDAs treatment [ 36 ]. Upregulation of HIF-1α was found in the prodromal state of AD, increasing the expression of several glycolytic enzymes, and is one mechanism by which astrocytes counteract the toxicity of Aβ [ 37 , 38 ]. However, the accumulation of Aβ and tau inhibited glycolysis, and this compensatory effect is lost in advanced AD [ 39 ], which was also proved in this study, resulting in an energy-deficient state and exacerbating oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

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

Zheng

Xie

Ren

et al. 2021

Molecular Metabolism

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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 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 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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Section: Discussionmentioning

confidence: 99%

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

Zheng

Xie

Ren

et al. 2021

Molecular Metabolism

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“…In particular, IL-1β and sICAM-1 were the most significantly increased. IL-1β has been previously shown to induce reactive astrogliosis [ 10 ], to be released by reactive astrocytes and astrocytes from 5xFAD AD mouse model [ 65 , 66 ], and to contribute to astrocyte-mediated neuronal death [ 67 ]; moreover, its levels are increased in AD brains [ 27 , 68 ]. ICAM-1 is a transmembrane glycoprotein belonging to the immunoglobulin family of adhesion molecules, expressed not only by endothelial and immune system cells [ 69 ] but also by astrocytes [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Oxysterols present in Alzheimer's disease brain induce synaptotoxicity by activating astrocytes: A major role for lipocalin-2

et al. 2021

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Among Alzheimer's disease (AD) brain hallmarks, the presence of reactive astrocytes was demonstrated to correlate with neuronal loss and cognitive deficits. Evidence indeed supports the role of reactive astrocytes as mediators of changes in neurons, including synapses. However, the complexity and the outcomes of astrocyte reactivity are far from being completely elucidated. Another key role in AD pathogenesis is played by alterations in brain cholesterol metabolism. Oxysterols (cholesterol oxidation products) are crucial for brain cholesterol homeostasis, and we previously demonstrated that changes in the brain levels of various oxysterols correlate with AD progression. Moreover, oxysterols have been shown to contribute to various pathological mechanisms involved in AD pathogenesis. In order to deepen the role of oxysterols in AD, we investigated whether they could contribute to astrocyte reactivity, and consequently impact on neuronal health. Results showed that oxysterols present in mild or severe AD brains induce a clear morphological change in mouse primary astrocytes, accompanied by the upregulation of some reactive astrocyte markers, including lipocalin-2 (Lcn2). Moreover, astrocyte conditioned media analysis revealed a significant increase in the release of Lcn2, cytokines, and chemokines in response to oxysterols. A significant reduction of postsynaptic density protein 95 (PSD95) and a concurrent increase in cleaved caspase-3 protein levels have been demonstrated in neurons co-cultured with oxysterol-treated astrocytes, pointing out that mediators released by astrocytes have an impact on neurons. Among these mediators, Lcn2 has been demonstrated to play a major role on synapses, affecting neurite morphology and decreasing dendritic spine density. These data demonstrated that oxysterols present in the AD brain promote astrocyte reactivity, determining the release of several mediators that affect neuronal health and synapses. Lcn2 has been shown to exert a key role in mediating the synaptotoxic effect of oxysterol-treated astrocytes.

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“…Moreover, a system-level represents one of the key tools to examine the transcriptional, post-translational, and epigenetic profiles (Blencowe et al, 2019). Regarding astrocytes, some multi-omic approaches have been done in the context of diseases such as Alzheimer neuroinflammation and glioblastoma (Currais et al, 2015;van Gijsel-Bonnello et al, 2018;Rosenberg et al, 2017;González-Ruiz et al, 2019;Rocchio et al, 2019). For example, Rocchio et al (2019) combined shotgun proteomics, genetic expression, calcium signaling, and a computational protein network from immortalized hippocampal astrocytes to establish a highly refined model of AD.…”

Section: Ependymalmentioning

confidence: 99%

Advances in Astrocyte Computational Models: From Metabolic Reconstructions to Multi-omic Approaches

González

Pinzón

Angarita-Rodríguez

et al. 2020

Front. Neuroinform.

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The growing importance of astrocytes in the field of neuroscience has led to a greater number of computational models devoted to the study of astrocytic functions and their metabolic interactions with neurons. The modeling of these interactions demands a combined understanding of brain physiology and the development of computational frameworks based on genomic-scale reconstructions, system biology, and dynamic models. These computational approaches have helped to highlight the neuroprotective mechanisms triggered by astrocytes and other glial cells, both under normal conditions and during neurodegenerative processes. In the present review, we evaluate some of the most relevant models of astrocyte metabolism, including genome-scale reconstructions and astrocyte-neuron interactions developed in the last few years. Additionally, we discuss novel strategies from the multi-omics perspective and computational models of other glial cell types that will increase our knowledge in brain metabolism and its association with neurodegenerative diseases.

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Correction: Metabolic changes and inflammation in cultured astrocytes from the 5xFAD mouse model of Alzheimer's disease: Alleviation by pantethine

Abstract: Metabolic changes and inflammation in cultured astrocytes from the 5xFAD mouse model of Alzheimer's disease: Alleviation by pantethine. PLoS ONE 12(4): e0175369.

Cited by 20 publications

References 2 publications

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

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

Oxysterols present in Alzheimer's disease brain induce synaptotoxicity by activating astrocytes: A major role for lipocalin-2

Advances in Astrocyte Computational Models: From Metabolic Reconstructions to Multi-omic Approaches

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