title: Down-regulation of astrocytic GLAST by microglia-related inflammation is abrogated in dibutyryl cAMP-differentiated cultures.
abstract: The influence of neuroinflammation on glutamate uptake by glial cells was examined after exposing primary cultures of rat astrocytes to conditioned culture medium from lipopolysaccharide-activated microglia. While such treatment triggered an inflammatory response in astrocytes, as revealed by the induction of cytokine expression, a significant decrease in GLAST expression and activity was observed after 72 h. This regulation of glutamate transporter was not observed with medium from naive microglia, but was mimicked by direct addition of tumor necrosis factor-alpha (TNF-alpha), a major cytokine released from activated microglia. Hence, on its own, TNF-alpha also triggered inflammation in astrocyte cultures, highlighting complex cross-talk between astrocytes and microglia in inflammatory conditions. This putatively detrimental regulation of GLAST in response to inflammation was also studied in cells exposed to dibutyryl cAMP, recognized as a model of astrocytes exhibiting a typical differentiated or activated phenotype. In this model, the conditioned culture medium from activated microglia, as well as TNF-alpha, were found to increase glutamate uptake capacity. Consistently, both of these treatments caused only modest induction of an inflammatory response in dibutyryl cAMP-matured astrocytes as compared to undifferentiated astrocytes. Together, these results suggest that differentiated/activated astrocytes are endowed with the capacity to confront inflammatory insults and that drugs influencing the astrocytes phenotype would deserve further consideration in the treatment of neurological disorders.
authors.affiliation: Laboratoire de Pharmacologie Expérimentale, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Tilleux
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Hermans
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003994:Bucladesine / Q000494:pharmacology* / Q000633:toxicity; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000494:pharmacology* / Q000633:toxicity; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D018836:Inflammation Mediators; C493392:Slc1a3 protein, rat; D003994:Bucladesine