Astrocytes aged in vitro show a decreased neuroprotective capacity
Open accessAbstract
Alterations in astrocyte function that may affect neuronal viability occur with brain aging. In this study, we evaluate the neuroprotective capacity of astrocytes in an experimental model of in vitro aging. Changes in oxidative stress, glutamate uptake and protein expression were evaluated in rat cortical astrocytes cultured for 10 and 90 days in vitro (DIV). Levels of glial fibrillary acidic protein and S100β increased at 90 days when cells were positive for the senescence β‐galactosidase marker. In long‐term astrocyte cultures, the generation of reactive oxygen species was enhanced and mitochondrial activity decreased. Simultaneously, there was an increase in proteins that stained positively for nitrotyrosine. The expression of Cu/Zn‐superoxide dismutase (SOD‐1) and haeme oxygenase‐1 (HO‐1) proteins and inducible nitric oxide synthase (iNOS) increased in aged astrocytes. Glutamate uptake in 90‐DIV astrocytes was higher than in 10 DIV ones, and was more vulnerable to inhibition by H 2 O 2 exposure. Enhanced glutamate uptake was probably because of up‐regulation of the glutamate/aspartate transporter protein. Aged astrocytes had a reduced ability to maintain neuronal survival. These findings indicate that astrocytes may partially loose their neuroprotective ability during aging. The results also suggest that aged astrocytes may contribute to exacerbating neuronal injury in age‐related neurodegenerative processes.
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Cultured rat astrocytes show characteristics of senescence, such as increased SA-β-gal staining, robust ROS production and decreased mitochondrial activity, resulting in loss of their ability to maintain neurons and detrimental effects in the aging brain.
“It has been reported that cultured rat astrocytes show characteristics of senescence, such as increased SA-β-gal staining, robust ROS production and decreased mitochondrial activity, resulting in the loss of their ability to maintain neurons and therefore exerting detrimental effects in the aging brain [137,138].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [137]
Astrocytic senescence has been reported in brains of aged animals, indicating a correlation between brain ageing and astrocytic senescence.
“Furthermore, astrocytic senescence has been reported in brains of aged animals [118, 124], indicating that there is a correlation between brain ageing and astrocytic senescence.”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [124]
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Research works printed but not linked: 9
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- Authors
- Pertusa, M., García‐Matas, S., Rodríguez‐Farré, E., Sanfeliu, C., & Cristòfol, R.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Cristòfol, R.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-01-23
- Volume
- 101
- Issue
- 3
- Pages
- 794-805
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1929217987
- Cited by
- 168
- References
- 0
- Citations by year
- 2026: 4 · 2025: 19 · 2024: 9 · 2023: 13 · 2022: 9 · 2021: 12 · 2020: 12 · 2019: 8 · 2018: 8 · 2017: 7 · 2016: 8 · 2015: 9 · 2014: 7 · 2013: 7 · 2012: 7
- FWCI
- 4.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Generalitat de Catalunya
- Departament d'Universitats, Recerca i Societat de la Informació
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- neuroprotection, brain aging, oxidative stress, reactive oxygen species, glutamate uptake, GLAST, nitrotyrosine, SOD1, heme oxygenase-1, inducible nitric oxide synthase, mitochondrial activity, glial fibrillary acidic protein, S100β, neuronal survival, age-related neurodegeneration
- MeSH terms
- Superoxide Dismutase-1, Aging, Animals, Animals, Newborn, Astrocytes, Cell Survival, Cells, Cultured, Cerebral Cortex, Dose-Response Relationship, Drug, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Hydrogen Peroxide, Nerve Growth Factors, S100 Proteins, Superoxide Dismutase, Tyrosine, Reactive Oxygen Species, Oxidative Stress, Glutamic Acid, Excitatory Amino Acid Transporter 1, Rats, Heme Oxygenase-1, Nitric Oxide Synthase Type II, S100 Calcium Binding Protein beta Subunit
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