title: HIV-1 gp120-induced axonal injury detected by accumulation of β-amyloid precursor protein in adult rat corpus callosum.
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.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Jingdong
authors.initials: J
authors.lastname: Zhang
authors.forename: Jianuo
authors.initials: J
authors.lastname: Liu
authors.forename: Bryan
authors.initials: B
authors.lastname: Katafiasz
authors.forename: Howard
authors.initials: H
authors.lastname: Fox
authors.forename: Huangui
authors.initials: H
authors.lastname: Xiong
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D015153:Blotting, Western; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4; C514793:gp120 protein, Human immunodeficiency virus 1