Journal of Neuroimmune Pharmacology

, Volume 6, Issue 4, pp 650–657

HIV-1 gp120-Induced Axonal Injury Detected by Accumulation of β-Amyloid Precursor Protein in Adult Rat Corpus Callosum

Authors

  • Jingdong Zhang
    • Department of Pharmacology and Experimental NeuroscienceUniversity of Nebraska Medical Center
  • Jianuo Liu
    • Department of Pharmacology and Experimental NeuroscienceUniversity of Nebraska Medical Center
  • Bryan Katafiasz
    • Department of Pharmacology and Experimental NeuroscienceUniversity of Nebraska Medical Center
  • Howard Fox
    • Department of Pharmacology and Experimental NeuroscienceUniversity of Nebraska Medical Center
    • Department of Pharmacology and Experimental NeuroscienceUniversity of Nebraska Medical Center
ORIGINAL ARTICLE

DOI: 10.1007/s11481-011-9259-6

Cite this article as:
Zhang, J., Liu, J., Katafiasz, B. et al. J Neuroimmune Pharmacol (2011) 6: 650. doi:10.1007/s11481-011-9259-6

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.

Keywords

HIV-1 gp120Axonal injuryCorpus callosumCXCR4β-Amyloid precursor proteinWhite matter damage

Copyright information

© Springer Science+Business Media, LLC 2011