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Journal of Neuroimmune Pharmacology

, Volume 11, Issue 1, pp 192–213 | Cite as

Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques

  • Liz Simon
  • Keijing Song
  • Curtis Vande Stouwe
  • Andrew Hollenbach
  • Angela Amedee
  • Mahesh Mohan
  • Peter Winsauer
  • Patricia MolinaEmail author
ORIGINAL ARTICLE

Abstract

Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing. Among the 24 miRs that were differentially expressed among the four groups, 16 miRs were modulated by THC in the presence of SIV. These 16 miRs were classified into four categories and the biological processes enriched by the target genes determined. Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques. This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group. Whether Δ9-THC-mediated modulation of epigenetic mechanisms provides neuroprotection in other regions of the brain and during chronic SIV-infection remains to be determined.

Keywords

SIV Cannabinoids Striatum miRNA 

Notes

Acknowledgments

This study was supported by National Institutes of Health grants: R01 DA030053 (NIH/NIDA), P60AA09803 (Analytical Core Laboratory LSUHSC Alcohol Research Center) and OD011104 (formerly RR00164). We acknowledge the scientific and technical expertise of John Maxi, graduate student at LSUHSC-NO, in dissecting the striatum from the brains. The authors would like to thank Drs. Ronald S. Veazey and Andrew A. Lackner for their scientific expertise. The authors also acknowledge Maurice Duplantis, Yun Te Lin, Faith R. Schiro and Cecily C. Midkiff for their technical assistance in the study.

Supplementary material

11481_2015_9645_MOESM1_ESM.docx (17 kb)
Supplemental Table 1 (DOCX 16 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Liz Simon
    • 1
  • Keijing Song
    • 2
  • Curtis Vande Stouwe
    • 2
  • Andrew Hollenbach
    • 3
  • Angela Amedee
    • 4
  • Mahesh Mohan
    • 5
  • Peter Winsauer
    • 6
  • Patricia Molina
    • 1
    Email author
  1. 1.Department of Physiology, Alcohol and Drug Abuse Center of ExcellenceLouisiana State University Health SciencesNew OrleansUSA
  2. 2.Department of PhysiologyLouisiana State University Health Sciences CenterNew OrleansUSA
  3. 3.Department of GeneticsLouisiana State University Health Sciences CenterNew OrleansUSA
  4. 4.Department of Microbiology, Immunology, & Parasitology; Alcohol and Drug Abuse Center of ExcellenceLouisiana State University Health Sciences CenterNew OrleansUSA
  5. 5.Department of Comparative PathologyTulane National Primate Research CenterCovingtonUSA
  6. 6.Department of Pharmacology; Alcohol and Drug Abuse Center of ExcellenceLouisiana State University Health Sciences CenterNew OrleansUSA

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