HIV-1 infected and immune competent mononuclear phagocytes induce quantitative alterations in neuronal dendritic arbor: Relevance for HIV-1-associated dementia

被引：28

作者：

Zheng, Jialin ^{[1
,2
,5
]}

Thylin, Michael R. ^{[1
,2
]}

Cotter, Robin L. ^{[1
,2
]}

Lopez, Alicia L. ^{[1
,2
]}

Ghorpade, Anuja ^{[1
,2
]}

Persidsky, Yuri ^{[1
,2
]}

Xiong, Huangui ^{[1
,2
]}

Leisman, Gary B. ^{[1
,2
]}

Che, My Hanh ^{[1
,2
]}

Gendelman, Howard E. ^{[1
,2
,3
,4
]}

机构：

[1] Univ Nebraska Med Ctr, Ctr Neurovirol & Neurodegenerat Disorders, Omaha, NE 68198 USA

[2] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA

[3] Univ Nebraska Med Ctr, Dept Med, Omaha, NE 68198 USA

[4] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA

[5] Ctr Neurovirol & Neurodegenerat Disorders, 985215 Nebraska Med Ctr, Omaha, NE 68198 USA

来源：

NEUROTOXICITY RESEARCH | 2001年 / 3卷 / 05期

基金：

美国国家卫生研究院;

关键词：

Human Immunodeficiency Virus Type; Neuronal Injury; Acquire Immune Deficiency Syndrome; Neurobasal Medium; Neuronal Viability;

D O I：

10.1007/BF03033203

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Neuronal loss, alterations in dendritic arbor, and decreased synaptic density, in infected brain tissue, are neuropathological signatures of HIV-1-associated dementia (HAD). Brain mononuclear phagocyte (MP) (macrophage and microglia) secretory products can effect neuronal compromise, although the underlying mechanism(s) remain incompletely defined. To these ends, we quantitatively assessed the effects of virus-infected and/or immune activated MP secretory products on multiple aspects of neuronal morphology. Rat cortical and hippocampal neurons were exposed to secretory products from HIV-1-infected and lipopolysaccharide (LPS)-activated human monocyte-derived macrophage (MDM). Our assays for alterations in neuronal dendritic arbor and cell loss included the quantification of neurofilament (NF), neuron-specific enolase (NSE), and MAP-2 by ELISA and cellular morphology. MDM conditioned media (MCM) enhanced neuronal survival. HIV-1 infection or activation by LPS had modest neurotoxic effects. In contrast, the combination of HIV-1 infection and activation of MDM produced significant neurotoxicity. Such MDM products altered dendritic arbor, decreased synaptic density, and increased LDH release. Comparable neurotrophic/toxic responses were observed when neurons were exposed to MCM collected from 12 separate human donors. Similar responses were observed with MCM from human fetal microglia, further supporting the role of HIV-1-infected and immune-activated brain MP in the overall neurotoxic responses. This work provides quantitative measures of neuronal damage by which virus infected and activated MP can elicit neuronal injury in HAD.

引用

页码：443 / 459

页数：17

共 43 条

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