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

Overview

Journal J Neurovirol

Publisher Springer

Specialties Microbiology
Neurology

Date 2017 May 3

PMID 28462488

Citations 7

Authors

Jessica R Lakritz

Samshita Yalamanchili

Michael J Polydefkis

Andrew D Miller

Michael S McGrath

Kenneth C Williams

Tricia H Burdo

Affiliations

Soon will be listed here.

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.

Citing Articles

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Nageotte nodules in human DRG reveal neurodegeneration in painful diabetic neuropathy.

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