title: Paroxetine prevented the down-regulation of astrocytic L-Glu transporters in neuroinflammation.
abstract: The extracellular L-glutamate (L-Glu) concentration is elevated in neuroinflammation, thereby causing excitotoxicity. One of the mechanisms is down-regulation of astrocyte L-Glu transporters. Some antidepressants have anti-inflammatory effects. We therefore investigated effects of various antidepressants on the down-regulation of astrocyte L-Glu transporters in the in vitro neuroinflammation model. Among these antidepressants, only paroxetine was effective. We previously demonstrated that the down-regulation of astrocyte L-Glu transporters was caused by L-Glu released from activated microglia. We here clarified that only paroxetine inhibited L-Glu release from microglia. This is the novel action of paroxetine, which may bring advantages on the therapy of neuroinflammation.
authors.affiliation: Laboratory of Neuropharmacology, Division of Pharmacology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan; Division of Basic Biological Science, Faculty of Pharmacy, Keio University, 1-5-30 Shiba-koen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Fujimori
authors.affiliation: Laboratory of Neuropharmacology, Division of Pharmacology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan; Division of Basic Biological Science, Faculty of Pharmacy, Keio University, 1-5-30 Shiba-koen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Takaki
authors.affiliation: Laboratory of Neuropharmacology, Division of Pharmacology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Shigemoto-Mogami
authors.affiliation: Laboratory of Neuropharmacology, Division of Pharmacology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sekino
authors.affiliation: Division of Basic Biological Science, Faculty of Pharmacy, Keio University, 1-5-30 Shiba-koen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Laboratory of Neuropharmacology, Division of Pharmacology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. Electronic address: kasato@nihs.go.jp.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sato
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000928:Antidepressive Agents / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008070:Lipopolysaccharides; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017374:Paroxetine / Q000494:pharmacology*
chemical_list: D027322:Amino Acid Transport System X-AG; D000928:Antidepressive Agents; D008070:Lipopolysaccharides; D018698:Glutamic Acid; D017374:Paroxetine
keywords: Inflammation; L-glutamate; Paroxetine