The HIV viral coat protein gp120 may induce AIDS dementia complex. A possible mechanism for gp120 penetration of the blood-brain barrier (BBB) involves transcytosis across the cells that separate the brain from the periphery. The long term goal of this study is to develop approaches that will block entry of HIV and gp120 into the brain by determining the pathways through which penetration occurs. They hypothesize that gp120 enters the endothelial cells of the BBB by adsorptive endocytosis and the resulting vesicles are routed to the Golgi complex, with some of the vesicularized gp120 transcytosed to the abluminal membranes and released into the parenchymal space of the brain. To test this hypothesis, we propose the following Specific Aims: 1) to determine in vivo in mice the gross anatomical distribution patterns of radioiodinated gp120 (I-gp120) within the brain by film autoradiography and computer-assisted image analysis after systemic administration; 2) To determine in vivo in mice the specific cellular associations of I- gp120 in brain tissues by emulsion autoradiography and immunohistochemistry after systemic administration; and 3) To determine in vivo in mice the subcellular vesicular routing of endocytosed horseradish peroxidase-labeled gp120 by electron microscopy after systemic administration.
| Maness, L M; Banks, W A; Kastin, A J (2000) Persistence of blood-to-brain transport of leptin in obese leptin-deficient and leptin receptor-deficient mice. Brain Res 873:165-7 |
