PMID- 23660833
OWN - NLM
STAT- MEDLINE
DCOM- 20140411
LR  - 20211021
IS  - 1557-1904 (Electronic)
IS  - 1557-1890 (Print)
IS  - 1557-1890 (Linking)
VI  - 8
IP  - 4
DP  - 2013 Sep
TI  - Enhancement of NMDA receptor-mediated excitatory postsynaptic currents by 
      gp120-treated macrophages: implications for HIV-1-associated neuropathology.
PG  - 921-33
LID - 10.1007/s11481-013-9468-2 [doi]
AB  - A plethora of prior studies has linked HIV-1-infected 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 monocyte-derived-macrophages (MDM) for its abilities to 
      affect NMDAR-mediated excitatory postsynaptic currents (EPSC(NMDAR)) in rat 
      hippocampal slices. Bath application of gp120-treated MDM-conditioned media (MCM) 
      produced an increase of EPSC(NMDAR). In contrast, control (untreated) MCM had 
      limited effects on EPSC(NMDAR). Testing NR2A NMDAR (NR2AR)-mediated EPSC 
      (EPSC(NR2AR)) and NR2B NMDAR (NR2BR)-mediated EPSC (EPSC(NR2BR)) for MCM showed 
      significant increased EPSC(NR2BR) when compared to EPSC(NR2AR) enhancement. When 
      synaptic NR2AR-mediated EPSC was blocked by bath application of MK801 combined 
      with low frequency stimulations, MCM retained its ability to enhance EPSC(NMDAR) 
      evoked by stronger stimulations. This suggested that increase in EPSC(NMDAR) was 
      mediated, in part, through extra-synaptic NR2BR. Further analyses revealed that 
      the soluble factors with low (<3 kD) to medium (3-10 kD) molecular weight 
      mediated the observed increases in EPSC(NMDAR). The link between activation of 
      NR2BRs and HIV-1gp120 MCM for neuronal injury was demonstrated by NR2BR but not 
      NR2AR blockers. Taken together, these results indicate that macrophage secretory 
      products induce neuronal injury through extra-synaptic NR2BRs.
FAU - Yang, Jianming
AU  - Yang J
AD  - Department of Pharmacology and Experimental Neuroscience, University of Nebraska 
      Medical Center, Omaha, NE 68198-5880, USA.
FAU - Hu, Dehui
AU  - Hu D
FAU - Xia, Jianxun
AU  - Xia J
FAU - Liu, Jianuo
AU  - Liu J
FAU - Zhang, Gang
AU  - Zhang G
FAU - Gendelman, Howard E
AU  - Gendelman HE
FAU - Boukli, Nawal M
AU  - Boukli NM
FAU - Xiong, Huangui
AU  - Xiong H
LA  - eng
GR  - R01 NS036126/NS/NINDS NIH HHS/United States
GR  - R01NS036126/NS/NINDS NIH HHS/United States
GR  - R01 NS063878/NS/NINDS NIH HHS/United States
GR  - R01NS063878/NS/NINDS NIH HHS/United States
GR  - P30 MH062261/MH/NIMH NIH HHS/United States
GR  - G12 MD007583/MD/NIMHD NIH HHS/United States
GR  - R01 NS077873/NS/NINDS NIH HHS/United States
GR  - 8G12 MD007583-27/MD/NIMHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130510
PL  - United States
TA  - J Neuroimmune Pharmacol
JT  - Journal of neuroimmune pharmacology : the official journal of the Society on 
      NeuroImmune Pharmacology
JID - 101256586
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (HIV Envelope Protein gp120)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (gp120 protein, Human immunodeficiency virus 1)
SB  - IM
MH  - Animals
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Excitatory Postsynaptic Potentials/drug effects/*physiology
MH  - Female
MH  - HIV Envelope Protein gp120/*toxicity
MH  - HIV-1/drug effects/*physiology
MH  - Hippocampus/drug effects/physiology
MH  - Humans
MH  - Macrophages/drug effects/pathology/*physiology
MH  - Male
MH  - Organ Culture Techniques
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*physiology
PMC - PMC3740075
MID - NIHMS478438
EDAT- 2013/05/11 06:00
MHDA- 2014/04/12 06:00
PMCR- 2014/09/01
CRDT- 2013/05/11 06:00
PHST- 2012/05/14 00:00 [received]
PHST- 2013/04/24 00:00 [accepted]
PHST- 2013/05/11 06:00 [entrez]
PHST- 2013/05/11 06:00 [pubmed]
PHST- 2014/04/12 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - 10.1007/s11481-013-9468-2 [doi]
PST - ppublish
SO  - J Neuroimmune Pharmacol. 2013 Sep;8(4):921-33. doi: 10.1007/s11481-013-9468-2. 
      Epub 2013 May 10.