Astrocyte Transforming Growth Factor Beta 1 Protects Synapses against Aβ Oligomers in Alzheimer's Disease Model
Open accessAbstract
Alzheimer's disease (AD) is characterized by progressive cognitive decline, increasingly attributed to neuronal dysfunction induced by amyloid-β oligomers (AβOs). Although the impact of AβOs on neurons has been extensively studied, only recently have the possible effects of AβOs on astrocytes begun to be investigated. Given the key roles of astrocytes in synapse formation, plasticity, and function, we sought to investigate the impact of AβOs on astrocytes, and to determine whether this impact is related to the deleterious actions of AβOs on synapses. We found that AβOs interact with astrocytes, cause astrocyte activation and trigger abnormal generation of reactive oxygen species, which is accompanied by impairment of astrocyte neuroprotective potential in vitro We further show that both murine and human astrocyte conditioned media (CM) increase synapse density, reduce AβOs binding, and prevent AβO-induced synapse loss in cultured hippocampal neurons. Both a neutralizing anti-transforming growth factor-β1 (TGF-β1) antibody and siRNA-mediated knockdown of TGF-β1, previously identified as an important synaptogenic factor secreted by astrocytes, abrogated the protective action of astrocyte CM against AβO-induced synapse loss. Notably, TGF-β1 prevented hippocampal dendritic spine loss and memory impairment in mice that received an intracerebroventricular infusion of AβOs. Results suggest that astrocyte-derived TGF-β1 is part of an endogenous mechanism that protects synapses agains…
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Mitochondrial dysfunction in astrocytes contributes to age-related neurodegenerative diseases and cognitive decline.
“Emerging evidence suggests that mitochondrial dysfunction in astrocytes contributes to age-related neurodegenerative diseases and cognitive decline (Diniz et al., 2017; Diniz et al., 2019a; Matias et al., 2022; Popov et al., 2023; Diniz et al., 2024a).”
From Aging promotes an increase in mitochondrial fragmentation in astrocytes (2024) · cites this paper as Diniz et al., 2017
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- Authors
- Pereira Diniz, L., Tortelli, V., Matias, I., Morgado, J., Bérgamo Araujo, A. P., Melo, H. M., Seixas da Silva, G. S., Alves-Leon, S. V., de Souza, J. M., Ferreira, S. T., De Felice, F. G., & Gomes, F. C. A.
- Affiliations
- Universidade Federal do Rio de Janeiro (BR)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2017-06-12
- Volume
- 37
- Issue
- 28
- Pages
- 6797-6809
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6596548
- OpenAlex
- W2625921226
- Cited by
- 171
- References
- 15
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 20 · 2023: 19 · 2022: 25 · 2021: 26 · 2020: 20 · 2019: 22 · 2018: 12 · 2017: 6
- FWCI
- 11.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Alzheimer's disease, amyloid-beta oligomers, astrocytes, TGF-β1, synaptic loss, synaptotoxicity, astrocyte activation, reactive oxygen species, astrocyte-conditioned medium, dendritic spine loss, memory impairment, hippocampal neurons, neuroprotection, siRNA knockdown, intracerebroventricular infusion
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Cells, Cultured, Humans, Male, Synapses, Amyloid beta-Peptides, Reactive Oxygen Species, Mice, Transforming Growth Factor beta1
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