HIV-1 gp120-induced axonal injury detected by accumulation of β-amyloid precursor protein in adult rat corpus callosum

Jingdong Zhang, Jianuo Liu, Bryan Katafiasz, Howard Fox, Huangui Xiong

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

HIV-1 brain infection induces neurodegeneration. While most studies focus on HIV-1-mediated neuronal injury, relatively few have investigated HIV-1-associated white matter damage. Corpus callosum (CC) is one of frequently involved white matter structures in HIV-1-associated white matter damage. Utilizing a model of ex vivo treatment of brain slice containing CC with HIV-1 glycoprotein 120 (gp120), we examined axonal injury by analyzing β-amyloid precursor protein (β-APP) accumulation in the axon. Incubation of CC slice with gp120 produced a significant higher density of β-APP in the CC tissue compared with non-gp120-treated controls, suggesting the presence of axonal damage in the CC. The gp120-induced CC axonal damage was blocked by a chemokine CXCR4 receptor antagonist T140 but not by an NMDA receptor blocker MK801 as demonstrated by Western blot analysis of β-APP, indicating that gp120 evokes the CC axonal injury through CXCR4 receptor. Immunocytochemical studies revealed a surprisingly high density of CXCR4-positive immunoreactivity in the CC. The CXCR4-positive labeling was distributed along the nerve fibers. Moreover, double labeling of anti-CXCR4 with either anti-neuronal nuclei or anti-myelin/oligodendrocyte-specific protein antibody revealed co-localization of CXCR4 and myelin/oligodendrocytes in some fiber-like structures, inferring that some neurons and oligodendrocytes in the CC express CXCR4. Taken together, these results indicate that gp120 induced axonal damage via CXCR4 in the CC.

Original languageEnglish (US)
Pages (from-to)650-657
Number of pages8
JournalJournal of Neuroimmune Pharmacology
Volume6
Issue number4
DOIs
StatePublished - Dec 2011

Keywords

  • Axonal injury
  • CXCR4
  • Corpus callosum
  • HIV-1 gp120
  • White matter damage
  • β-Amyloid precursor protein

ASJC Scopus subject areas

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

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