HIV-1 Tat and Cocaine Impair Survival of Cultured Primary Neuronal Cells via a Mitochondrial Pathway

Francesca Isabella De Simone, Nune Darbinian, Shohreh Amini, Madesh Muniswamy, Martyn K. White, John W. Elrod, Prasun K. Datta, Dianne Langford, Kamel Khalili

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Addictive stimulant drugs, such as cocaine, are known to increase the risk of exposure to HIV-1 infection and hence predispose towards the development of AIDS. Previous findings suggested that the combined effect of chronic cocaine administration and HIV-1 infection enhances cell death. Neuronal survival is highly dependent on the health of mitochondria providing a rationale for assessing mitochondrial integrity and functionality following cocaine treatment, either alone or in combination with the HIV-1 viral protein Tat, by monitoring ATP release and mitochondrial membrane potential (ΔΨm). Our results indicate that exposing human and rat primary hippocampal neurons to cocaine and HIV-1 Tat synergistically decreased both mitochondrial membrane potential and ATP production. Additionally, since previous studies suggested HIV-1 infection alters autophagy in the CNS, we investigated how HIV-1 Tat and cocaine affect autophagy in neurons. The results indicated that Tat induces an increase in LC3-II levels and the formation of Parkin-ring-like structures surrounding damaged mitochondria, indicating the possible involvement of the Parkin/PINK1/DJ-1 (PPD) complex in neuronal degeneration. The importance of mitochondrial damage is also indicated by reductions in mitochondrial membrane potential and ATP content induced by HIV-1 Tat and cocaine.

Original languageEnglish (US)
Pages (from-to)358-368
Number of pages11
JournalJournal of Neuroimmune Pharmacology
Volume11
Issue number2
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Keywords

  • Autophagy
  • Cocaine
  • HIV-1 Tat
  • Mitochondria
  • Mitophagy
  • Neurodegeneration
  • Neuronal Cells
  • ROS

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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  • Cite this

    De Simone, F. I., Darbinian, N., Amini, S., Muniswamy, M., White, M. K., Elrod, J. W., Datta, P. K., Langford, D., & Khalili, K. (2016). HIV-1 Tat and Cocaine Impair Survival of Cultured Primary Neuronal Cells via a Mitochondrial Pathway. Journal of Neuroimmune Pharmacology, 11(2), 358-368. https://doi.org/10.1007/s11481-016-9669-6