Neuronal Survival and Resistance to HIV-1 Tat Toxicity in the Primary Culture of Rat Fetal Neurons

Overview

Journal Exp Neurol

Specialty Neurology

Date 2008 Nov 18

PMID 19013459

Citations 23

Authors

Marina V Aksenova

Michael Y Aksenov

Sheila M Adams

Charles F Mactutus

Rosemarie M Booze

Affiliations

Soon will be listed here.

Abstract

In this study we report that primary cultures of rat fetal neurons contain subpopulations of cells that may be sensitive or resistant to HIV-1 Tat neurotoxicity. We demonstrate that rapid binding/uptake of Tat 1-86 for 2 h was sufficient to trigger caspase activation and neurodegeneration in rat fetal midbrain cell cultures. The uptake of Tat was followed by an increase in MCP1 (CCL2) immunoreactivity. Approximately 70% of neurons were able to survive transient or continuous (7 days) Tat exposure. The surviving neurons did not contain bound/internalized Tat, but were able to interact with Tat after medium replacement. These neurons were resistant to Tat toxicity. In neurons that resisted the toxic effects of continuous and repeated Tat treatment, levels of NR2A subunit of the NMDA receptor complex were significantly lower than in controls. We suggest that the subunit composition of NMDAR complexes may be important for the sensitivity of neurons to Tat toxicity.

Citing Articles

Suppression of HIV-TAT and cocaine-induced neurotoxicity and inflammation by cell penetrable itaconate esters.

Cui B, Aksenova M, Sikirzhytskaya A, Odhiambo D, Korunova E, Sikirzhytski V J Neurovirol. 2024; 30(4):337-352.

PMID: 38884890 PMC: 11512888. DOI: 10.1007/s13365-024-01216-9.

Suppression of HIV and cocaine-induced neurotoxicity and inflammation by cell penetrable itaconate esters.

Cui B, Aksenova M, Sikirzhytskaya A, Odhiambo D, Korunova E, Sikirzhytski V bioRxiv. 2023; .

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HIV-1 Tat: Role in Bystander Toxicity.

Ajasin D, Eugenin E Front Cell Infect Microbiol. 2020; 10:61.

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Inhibition of the Dead Box RNA Helicase 3 Prevents HIV-1 Tat and Cocaine-Induced Neurotoxicity by Targeting Microglia Activation.

Aksenova M, Sybrandt J, Cui B, Sikirzhytski V, Ji H, Odhiambo D J Neuroimmune Pharmacol. 2019; 15(2):209-223.

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HIV Infection Induces Extracellular Cathepsin B Uptake and Damage to Neurons.

Cantres-Rosario Y, Ortiz-Rodriguez S, Santos-Figueroa A, Plaud M, Negron K, Cotto B Sci Rep. 2019; 9(1):8006.

PMID: 31142756 PMC: 6541605. DOI: 10.1038/s41598-019-44463-1.

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