An oral form of methylglyoxal-bis-guanylhydrazone reduces monocyte activation and traffic to the dorsal root ganglia in a primate model of HIV-peripheral neuropathy

  • Jessica R. Lakritz
  • Samshita Yalamanchili
  • Michael J. Polydefkis
  • Andrew D. Miller
  • Michael S. McGrath
  • Kenneth C. Williams
  • Tricia H. Burdo
Article

DOI: 10.1007/s13365-017-0529-9

Cite this article as:
Lakritz, J.R., Yalamanchili, S., Polydefkis, M.J. et al. J. Neurovirol. (2017). doi:10.1007/s13365-017-0529-9
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Abstract

Peripheral neuropathy (PN) is a major comorbidity of HIV infection that is caused in part by chronic immune activation. HIV-PN is associated with infiltration of monocytes/macrophages to the dorsal root ganglia (DRG) causing neuronal loss and formation of Nageotte nodules. Here, we used an oral form of methylglyoxal-bis-guanylhydrazone (MGBG), a polyamine biosynthesis inhibitor, to specifically reduce activation of myeloid cells. MGBG is selectively taken up by monocyte/macrophages in vitro and inhibits HIV p24 expression and DNA viral integration in macrophages. Here, MGBG was administered to nine SIV-infected, CD8-depleted rhesus macaques at 21 days post-infection (dpi). An additional nine SIV-infected, CD8-depleted rhesus macaques were used as untreated controls. Cell traffic to tissues was measured by in vivo BrdU pulse labeling. MGBG treatment significantly diminished DRG histopathology and reduced the number of CD68+ and CD163+ macrophages in DRG tissue. The number of recently trafficked BrdU+ cells in the DRG was significantly reduced with MGBG treatment. Despite diminished DRG pathology, intraepidermal nerve fiber density (IENFD) did not recover after treatment with MGBG. These data suggest that MGBG alleviated DRG pathology and inflammation.

Keywords

HIV Rhesus Peripheral neuropathy Dorsal root ganglia Monocyte Polyamine biosynthesis inhibitor 

Copyright information

© Journal of NeuroVirology, Inc. 2017

Authors and Affiliations

  • Jessica R. Lakritz
    • 1
  • Samshita Yalamanchili
    • 1
  • Michael J. Polydefkis
    • 2
  • Andrew D. Miller
    • 3
  • Michael S. McGrath
    • 4
  • Kenneth C. Williams
    • 1
  • Tricia H. Burdo
    • 5
  1. 1.Department of BiologyBoston CollegeChestnut HillUSA
  2. 2.Department of NeurologyJohns Hopkins MedicineBaltimoreUSA
  3. 3.Department of Biomedical Sciences, Section of Anatomic PathologyCornell University College of Veterinary MedicineIthacaUSA
  4. 4.Departments of Laboratory Medicine, Medicine and PathologyUniversity of California at San FransciscoSan FranciscoUSA
  5. 5.Department of NeuroscienceTemple University School of MedicinePhiladelphiaUSA

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