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Neurochem Int ; 140: 104837, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32858088

RESUMO

Astrocytes play a key role by providing antioxidant support to nearby neurons under oxidative stress. We have previously demonstrated that in vitro astroglial subtype 3 metabotropic glutamate receptor (mGlu3R) is neuroprotective. However, its role during aging has been poorly explored. Our study aimed to determine whether LY379268, an mGlu3R agonist, exerts an antioxidant effect on aged cultured rat astrocytes. Aged cultured astrocytes obtained after 9-weeks (9w) in vitro were positive for ß-galactosidase stain, showed decreased mGlu3R and glutathione (GSH) levels and superoxide dismutase (SOD) activity, while nuclear erythroid factor 2 (Nrf2) protein levels, reactive oxygen species (ROS) production and apoptosis were increased. Treatment of 9w astrocytes with LY379268 resulted in an increase in mGlu3R and Nrf2 protein levels and SOD activity, and decreased mitochondrial ROS levels and apoptosis. mGlu3R activation in aged astrocytes also prevented hippocampal neuronal death induced by Aß1-42 in co-culture assays. We conclude that activation of mGlu3R in aged astrocytes had an anti-oxidant effect and protected hippocampal neurons against Aß-induced neurotoxicity. The present study suggests mGlu3R activation in aging astrocytes as a therapeutic strategy to slow down age-associated neurodegeneration.


Assuntos
Antioxidantes/farmacologia , Astrócitos/metabolismo , Senescência Celular/fisiologia , Fármacos Neuroprotetores/farmacologia , Receptores de Glutamato Metabotrópico/agonistas , Receptores de Glutamato Metabotrópico/metabolismo , Aminoácidos/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Técnicas de Cocultura , Feminino , Gravidez , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
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