Glioma-associated microglia and macrophages/monocytes display distinct electrophysiological properties and do not communicate via gap junctions

NEUROSCIENCE LETTERS

卷:583

Article

Richter, Nadine¹  Wendt, Stefan¹  Georgieva, Petya B.¹  Hambardzumyan, Dolores²  Nolte, Christiane¹  Kettenmann, Helmut¹ 

[1] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany

[2] Case Western Reserve Univ, Lerner Coll Med, Cleveland Clin, Dept Mol Med, Cleveland, OH 44106 USA

关键词: Glioma-associated microglia;    Glioma-associated;    macrophages/monocytes;    Glioma;    Gap junctions;    Electrophysiology;   

DOI  :  10.1016/j.neulet.2014.09.035

来源: Elsevier

【 摘 要 】

Both brain-resident microglia and peripheral macrophages/monocytes infiltrate into glioma and promote glioma growth. In the present study we analyzed coupling and membrane currents in glioma-associated microglia and macrophages/monocytes and compared this to control and stab wound-associated microglia. Using the Cx3cr1(GFP/wt) Ccr2(RFP/wt) knock-in mouse line, we distinguished membrane currents of glioma-associated microglia and macrophages/monocytes in acute brain slices prepared 14-16 days after inoculation of GL261 glioma cells. The current profile of microglia showed inward rectifying currents reminiscent of an intermediate activation state when compared to other disease models or cell culture. Macrophages/monocytes showed a higher specific outward conductance and a significantly lower capacitance indicative of a smaller membrane area than microglia. As controls, we also recorded currents from control microglia and stab wound-associated microglia. Since there are reports of microglial coupling in vitro, we injected biocytin into these cells and analyzed for cell coupling after fixing the slices and processed for biocytin labeling with Cy3-conjugated-Streptavidin. Neither control microglia nor glioma-associated microglia and macrophages/monocytes nor stab wound-associated microglia showed any sign of coupling. Moreover, performing qRT-PCR revealed that no connexin43 was detectable on isolated and sorted glioma-associated microglia and macrophages/monocytes, indicating that these cells are not part of a coupled network. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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