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Reduced ABC efflux transporter function in activated microglia: Implications in neurodegeneration
Author(s) -
Gibson Christopher,
Richardson Jason R.,
Aleksunes Lauren M.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.398.3
Subject(s) - microglia , efflux , transporter , neuroinflammation , calcein , neurodegeneration , neurotoxicity , chemistry , lipopolysaccharide , pharmacology , microbiology and biotechnology , biochemistry , biology , immunology , inflammation , medicine , toxicity , gene , disease , organic chemistry , membrane
Efflux transporters in the brain limit exposure to chemicals and potentially toxic endogenous products, which may be altered during neurodegeneration and contribute to further injury. The purpose of this study was to characterize ABC efflux transporter function in unstimulated mouse BV2 microglia and in microglia activated with lipopolysaccharide (LPS, E.coli ). Fluorescent substrates and known inhibitors were used to characterize the function of efflux transporters Resting microglia actively transported rhodamine 123, calcein AM, and Hoechst, which were blocked by inhibitors of MDR1 (PSC833), MRP (MK571), and BCRP (KO143), respectively. Activation of microglia with LPS significantly reduced transporter function, indicated by up to a 90% increase in cellular retention of rhodamine 123, Calcein AM, and Hoescht. Decreased efflux transporter function in activated microglia correlates with down‐regulation of transporter mRNA and protein levels. Collectively, these results suggest that microglia activation during neuroinflammation may impair normal regulatory functions of microglia including the efflux of potentially toxic compounds. NIH ES‐0205022, ES‐005022, ES‐015991, DK‐ 080774, ES‐007148.