[HIV-1gp120 injures neurons by alteration of neuronal expressions of NR2B and PSD-95].
OBJECTIVE
To investigate the mechanisms underlying HIV-1 envelope glycoprotein 120 (gp120)-associated neurotoxicity on rat cortical neuronal cultures.


METHODS
Experiments were carried out on primary cortical neuronal cultures prepared from fetal Sprague-Dawley fetal rats. Immunocytochemistry and Western blot techniques were employed to examine the changes of the expressions of N-methyl-D-asparate receptors 2B(NR2B) and postsynaptic density 95 (PSD-95) in cultured neurons in the presence and absence of gp120 in the culture media. Gp120-induced neurotoxicity was determined by MTT assay.


RESULTS
MTT assay showed gp120 produced dose-dependent neuronal injury when added to the culture media and the gp120-induced neuronal injury was blocked by memantine, a specific NR2B receptor antagonist. Further studies revealed that gp120 induced neuronal injury by up-regulation of NR2B and down-regulation of PSD-95 expressions in rat cortical neurons.


CONCLUSIONS
These results demonstrated that gp120 injures neurons via an increase of NR2B and a decrease of PSD-95 expressions. The gp120-induced neuronal injury can be blocked by a specific NR2B receptor antagonist, suggesting NR2B may function as a potential target for the development of therapeutic strategies.
Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Wenbi
W
Xiong
Key Laboratory of Molecular Medicine, Second Affiliated Hospital, Nanchang University, Nanchang 330006, China.
Jinyan
J
Xie
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880.
Jianuo
J
Liu
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880.
Huangui
H
Xiong
D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D015699:HIV Envelope Protein gp120 / Q000633:toxicity*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D015699:HIV Envelope Protein gp120; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C121001:NR2B NMDA receptor; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; C514793:gp120 protein, Human immunodeficiency virus 1