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gp120-Induced Neurotoxicity in Hippocampal Pyramidal Neuron Cultures: Protective Action of TGF-β1
Journal article   Open access   Peer reviewed

gp120-Induced Neurotoxicity in Hippocampal Pyramidal Neuron Cultures: Protective Action of TGF-β1

Olimpia Meucci and Richard J Miller
The Journal of neuroscience, v 16(13), pp 4080-4088
01 Jul 1996
PMID: 8753870
url
https://doi.org/10.1523/jneurosci.16-13-04080.1996View
Published, Version of Record (VoR)CC BY-NC-SA V4.0 Open
url
https://doi.org/10.1523/JNEUROSCI.16-13-04080.1996View
Published, Version of Record (VoR) Open

Abstract

HIV-1 AIDS intracellular calcium neurotoxicity cell death NMDA receptors
We found that TGF-β1, a cytokine that previously has been reported to have neuroprotective effects, was able to prevent the toxicity induced by the HIV-1 coat protein gp120 in hippocampal pyramidal neuron cultures. In the presence of glia, gp120 induced time- and dose-dependent cell death, which was more pronounced in mature (7-19 d in culture) than in young neurons (2-7 d in culture). Staining with nuclear dyes (propidium iodide and Hoechst 33342), in situ detection of DNA fragments, and DNA analysis on agarose gels indicated that apoptosis was mainly responsible for the death caused by the viral protein. However, after several days of treatment, deathdisplaying necrotic features also occurred. Neurotoxicity induced by gp120 was dependent on the activation of NMDA receptors and required the presence of glia as well as new protein synthesis. Thus, the effect of gp120 was abolished by the NMDA receptor antagonist APV and partially reduced by cycloheximide. Only modest neurotoxicity was observed in pure neuronal cultures deprived of the glia feeder layer. Fura-2-based videoimaging showed that treatment with gp120 enhanced the ability of NMDA to increase neuronal [Ca 2+ ] i . The impairment of neuronal Ca 2+ homeostasis was prevented completely by TGF-β1. Therefore, it is likely that the neuroprotective action of the cytokine is attributable to its ability to stabilize neuronal [Ca 2+ ] i .

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