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Astrocytes aged in vitro show a decreased neuroprotective capacity
Author(s) -
Pertusa M.,
GarcíaMatas S.,
RodríguezFarré E.,
Sanfeliu C.,
Cristòfol R.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04369.x
Subject(s) - neuroprotection , astrocyte , glutamate receptor , glial fibrillary acidic protein , superoxide dismutase , oxidative stress , biology , microbiology and biotechnology , nitric oxide synthase , nitric oxide , excitotoxicity , biochemistry , neuroscience , endocrinology , immunology , central nervous system , receptor , immunohistochemistry
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.