The Epigenetic Role of miR-124 in HIV-1 Tat- and Cocaine-Mediated Microglial Activation

Palsamy Periyasamy, Annadurai Thangaraj, Muthukumar Kannan, Abiola Oladapo, Shilpa Buch

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

HIV-1 and drug abuse have been indissolubly allied as entwined epidemics. It is well-known that drug abuse can hasten the progression of HIV-1 and its consequences, especially in the brain, causing neuroinflammation. This study reports the combined effects of HIV-1 Transactivator of Transcription (Tat) protein and cocaine on miR-124 promoter DNA methylation and its role in microglial activation and neuroinflammation. The exposure of mouse primary microglial cells to HIV-1 Tat (25 ng/mL) and/or cocaine (10 μM) resulted in the significantly decreased expression of primary (pri)-miR-124-1, pri-miR-124-2, and mature miR-124 with a concomitant upregulation in DNMT1 expression as well as global DNA methylation. Our bisulfite-converted genomic DNA sequencing also revealed significant promoter DNA methylation in the pri-miR-124-1 and pri-miR-124-2 in HIV-1 Tat- and cocaine-exposed mouse primary microglial cells. We also found the increased expression of proinflammatory cytokines such as IL1β, IL6 and TNF in the mouse primary microglia exposed to HIV-1 Tat and cocaine correlated with microglial activation. Overall, our findings demonstrate that the exposure of mouse primary microglia to both HIV-1 Tat and cocaine could result in intensified microglial activation via the promoter DNA hypermethylation of miR-124, leading to the exacerbated release of proinflammatory cytokines, ultimately culminating in neuroinflammation.

Original languageEnglish (US)
Article number15017
JournalInternational journal of molecular sciences
Volume23
Issue number23
DOIs
StatePublished - Dec 2022

Keywords

  • DNA methylation
  • HIV-1 Tat
  • HIV-1 associated neurocognitive disorders
  • cocaine
  • epigenetics
  • microglia
  • neuroinflammation

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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