AI Article Synopsis
- Impaired glutamate uptake by astrocytes is linked to neuronal damage in nervous disorders, often driven by inflammation associated with microglia.
- Exposure to inflammatory signals from activated microglia increases the expression and activity of the glutamate transporter GLT-1 in astrocytes.
- These findings indicate that microglia-induced inflammation can significantly regulate glutamate neurotransmission, affecting both normal and reactive astrocytes.
Article Abstract
Impaired glial glutamate uptake is commonly involved in neuronal damages observed in acute and chronic nervous disorders. As nervous insults are frequently associated with local inflammation involving microglia, this study aims at exploring the link between activated microglia and altered glutamate uptake in astrocytes. The regulation of the expression and activity of type 1 glutamate transporter (GLT-1) was examined after exposing cultures of rat astrocytes to conditioned medium from lipopolysaccharide-activated microglia cultures. Significant increases in GLT-1 mRNA expression and dihydrokainate sensitive uptake of aspartate were observed after 72h of treatment. These effects were reproduced by direct exposure of the astrocyte cultures to tumor necrosis factor alpha, a major cytokine released by activated microglia. The regulation of GLT-1 activity in response to inflammatory stimuli was also evidenced in cells exposed to dibutyryl cAMP, recognised as a model of reactive astrocytes in which the expression of this glutamate transporter is constitutively enhanced. Taken together, these results suggest that the GLT-1-dependent control of glutamate neurotransmission by either naive or chemically activated astrocytes is influenced by microglia-mediated inflammation.
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| http://dx.doi.org/10.1016/j.neuint.2008.12.021 | DOI Listing |
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