Inhibition of myelin formation by HIV-1 gp120 in rat cerebral cortex culture.
To study the role of HIV-1 gp120 in loss of myelin in HIV encephalopathy, the binding of gp120 to various types of neural cells and its effects on myelination were examined in rat primary brain culture. Double-staining of cultured cells with gp120 and specific antibodies for different neural cell types showed that gp120 bound to most of the galactocerebroside (GalC)-positive oligodendrocytes, a small population of type-2-like astrocytes and a few small neurons. Gp120 did not bind to type-1-like astrocytes, most neurons, or to macrophage/microglia. To assay myelination, cells were bathed in a myelination medium containing chick embryo extract and high glucose, with or without gp120. Seven days after the application, myelination in the culture was observed morphologically and by staining with anti-myelin basic protein (MBP) antibody, and was found to be significantly inhibited by the addition of gp120 (50-100 nM). The processes of oligodendrocytes were reduced in length and arborization relative to the control, but MBP production by oligodendrocytes was unaffected. These results show that gp120 can cause a functional disorder of oligodendrocytes and thus could underlie the diffuse loss of myelin sheaths of HIV encephalopathy.
Kimura-Kuroda
J
J
Department of Microbiology and Immunology, Tokyo Metropolitan Institute for Neuroscience, Japan.
Nagashima
K
K
Yasui
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D015153:Blotting, Western; D001921:Brain / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005699:Galactosylceramides / Q000378:metabolism; D015483:HIV Antibodies / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D015497:HIV-1; D008081:Liposomes; D008854:Microscopy, Electron; D004676:Myelin Basic Protein / Q000096:biosynthesis* / Q000302:isolation & purification; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D005699:Galactosylceramides; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D008081:Liposomes; D004676:Myelin Basic Protein; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha