Immunoregulation of a CB2 receptor agonist in a murine model of neuroaids

Santhi Gorantla, Edward Makarov, Deepa Roy, Jennifer Finke-Dwyer, L. Charles Murrin, Howard E. Gendelman, Larisa Poluektova

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Chronic HIV-1 infection commonly affects behavioral, cognitive, and motor functions in the infected human host and is commonly referred to as HIV-1-associated neurocognitive disorders (HAND). This occurs, in measure, as a consequence of ingress of leukocytes into brain perivascular regions. Such cells facilitate viral infection and disease by eliciting blood-brain barrier and neuronal network dysfunctions. Previous works demonstrated that the endocannabinoid system modulates neuroimmunity and as such neuronal and glial functions. Herein, we investigated CB2R receptor expression in murine HIV-1 encephalitis (HIVE) and the abilities of a highly selective CB2R agonist, Gp1a, to modulate disease. HIV-1-infected human monocyte-derived macrophages were injected into the caudate and putamen of immunodeficient mice reconstituted with human peripheral blood lymphocytes (hu-PBL/HIVE). Brains of hu-PBL/HIVE mice showed microglial activation and increased expression of CB2R, but not CB1R or GPR55. Gp1a substantively reduced infiltration of human cells into the mouse brain and reduced HLA DQ activation. Gp1a down modulated CCR5 expression on human cells in the spleen with an increase in Fas ligand expression. Our results support the notion that CB2 receptor agonists may be a viable therapeutic candidate for HAND.

Original languageEnglish (US)
Pages (from-to)456-468
Number of pages13
JournalJournal of Neuroimmune Pharmacology
Volume5
Issue number3
DOIs
StatePublished - Sep 2010

Keywords

  • CB2R
  • HIV-1-associated neurocognitive disorders
  • human immunodeficiency virus
  • neuroinflammation

ASJC Scopus subject areas

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

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