Journal of Neuroimmune Pharmacology

, Volume 5, Issue 3, pp 456–468

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
ORIGINAL ARTICLE

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.

Keywords

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

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Santhi Gorantla
    • 1
    • 2
  • Edward Makarov
    • 1
  • Deepa Roy
    • 1
  • Jennifer Finke-Dwyer
    • 1
  • L. Charles Murrin
    • 1
  • Howard E. Gendelman
    • 1
  • Larisa Poluektova
    • 1
  1. 1.Department of Pharmacology and Experimental NeuroscienceUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.Department of Pharmacology and Experimental Neuroscience985880 Nebraska Medical CenterOmahaUSA

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