Enhancement of NMDA Receptor-Mediated Excitatory Postsynaptic Currents by gp120-Treated Macrophages: Implications for HI
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ORIGINAL ARTICLE
Enhancement of NMDA Receptor-Mediated Excitatory Postsynaptic Currents by gp120-Treated Macrophages: Implications for HIV-1-Associated Neuropathology Jianming Yang & Dehui Hu & Jianxun Xia & Jianuo Liu & Gang Zhang & Howard E. Gendelman & Nawal M. Boukli & Huangui Xiong
Received: 14 May 2012 / Accepted: 24 April 2013 / Published online: 10 May 2013 # Springer Science+Business Media New York 2013
Abstract A plethora of prior studies has linked HIV-1infected and immune activated brain mononuclear phagocytes (MP; blood borne macrophages and microglia) to neuronal dysfunction. These are modulated by N-methyl-D-aspartate receptor (NMDAR) antagonists and supporting their relevance for HIV-1-associated nervous system disease. The role of NMDAR subsets in HIV-1-induced neuronal injury, nonetheless, is poorly understood. To this end, we investigated conditioned media from HIV-1gp120-treated human monocytederived-macrophages (MDM) for its abilities to affect NMDAR-mediated excitatory postsynaptic currents (EPSCNMDAR) in rat hippocampal slices. Bath application of J. Yang : D. Hu : J. Xia : J. Liu : G. Zhang : H. E. Gendelman : H. Xiong (*) Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA e-mail: [email protected] H. E. Gendelman Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA
gp120-treated MDM-conditioned media (MCM) produced an increase of EPSCNMDAR. In contrast, control (untreated) MCM had limited effects on EPSCNMDAR. Testing NR2A NMDAR (NR2AR)-mediated EPSC (EPSCNR2AR) and NR2B NMDAR (NR2BR)-mediated EPSC (EPSCNR2BR) for MCM showed significant increased EPSCNR2BR when compared to EPSCNR2AR enhancement. When synaptic NR2AR-mediated EPSC was blocked by bath application of MK801 combined with low frequency stimulations, MCM retained its ability to enhance EPSCNMDAR evoked by stronger stimulations. This suggested that increase in EPSCNMDAR was mediated, in part, through extra-synaptic NR2BR. Further analyses revealed that the soluble factors with low (
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