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Human immunodeficiency virus type-1 vulnerates nascent neuronal cells
Hiroko Kitayama,
Yoshiharu Miura,
Yoshinori Ando,
Yoshio Koyanagi,
Hiroko Kitayama
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan
Search for more papers by this authorYoshiharu Miura
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan
Search for more papers by this authorYoshinori Ando
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan
Search for more papers by this authorYoshio Koyanagi
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan
Search for more papers by this authorHiroko Kitayama,
Yoshiharu Miura,
Yoshinori Ando,
Yoshio Koyanagi,
Hiroko Kitayama
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan
Search for more papers by this authorYoshiharu Miura
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan
Search for more papers by this authorYoshinori Ando
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan
Search for more papers by this authorYoshio Koyanagi
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan
Search for more papers by this authorCorrespondence
Yoshio Koyanagi, Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, 53 Shogoin-kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Tel: +81-75-751-4811; fax: +81-75-751-4812; email: [email protected]
ABSTRACT
Macrophages or microglial cells are the major target cells for HIV-1 infection in the brain. The infected cells release neurotoxic factors that may cause severe neuronal cell damage, especially in the basal ganglia and hippocampus. In this study, we used rat OHC to examine the region-specific neuronal cell damage caused by HIV-1-infected macrophages. When OHC was cocultured with HIV-1-infected MDM, we found that neuronal cells at the GCL of the DG were preferentially killed via apoptosis, and that projection of MF from GCL to PCL of the CA3 region was severely disturbed. We marked precursor cells around the DG region by using an EGFP-expressing retrovirus vector and found that these cells lost the ability to differentiate into neurons when exposed to HIV-1-infected MDM. In the DG, new neurons are normally incorporated into GCL or PCL, while in the presence of HIV-1-infected MDM, mature neurons failed to be incorporated into those layers. These data indicate that the neurotoxic factor(s) released from HIV-1-infected macrophages impede(s) neuronal cell repair in brain tissue. This suggests that DG is the region of the hippocampus most vulnerable to neuronal damage caused by HIV-1 infection, and that its selective vulnerability is most likely due to the highly active neurogenesis that takes place in this region.
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