title: Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques.
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.
authors.affiliation: Department of Physiology, Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences, 1901 Perdido Street, Medical Education Building 7205, P7-3, New Orleans, LA, 70112, USA.
authors.forename: Liz
authors.initials: L
authors.lastname: Simon
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA, 70112, USA.
authors.forename: Keijing
authors.initials: K
authors.lastname: Song
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA, 70112, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Vande Stouwe
authors.affiliation: Department of Genetics, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA, 70112, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hollenbach
authors.affiliation: Department of Microbiology, Immunology, & Parasitology; Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA, 70112, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Amedee
authors.affiliation: Department of Comparative Pathology, Tulane National Primate Research Center, 18703 3 Rivers Rd, Covington, LA, 70433, USA.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Mohan
authors.affiliation: Department of Pharmacology; Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA, 70112, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Winsauer
authors.affiliation: Department of Physiology, Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences, 1901 Perdido Street, Medical Education Building 7205, P7-3, New Orleans, LA, 70112, USA. pmolin@lsuhsc.edu.
authors.forename: Patricia
authors.initials: P
authors.lastname: Molina
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003342:Corpus Striatum / Q000187:drug effects / Q000821:virology*; D013759:Dronabinol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D015213:Neuroimmunomodulation / Q000187:drug effects* / Q000502:physiology; D016133:Polymerase Chain Reaction; D060888:Real-Time Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus; D019562:Viral Load
chemical_list: D035683:MicroRNAs; D013759:Dronabinol
keywords: Cannabinoids; SIV; Striatum; miRNA