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Neurotoxicity Research

, Volume 3, Issue 5, pp 443–459 | Cite as

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

  • Jialin ZhengEmail author
  • Michael R. Thylin
  • Robin L. Cotter
  • Alicia L. Lopez
  • Anuja Ghorpade
  • Yuri Persidsky
  • Huangui Xiong
  • Gary B. Leisman
  • My Hanh Che
  • Howard E. Gendelman
Article

Abstract

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.

Keywords

Human Immunodeficiency Virus Type Neuronal Injury Acquire Immune Deficiency Syndrome Neurobasal Medium Neuronal Viability 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

AIDS

acquired immune deficiency syndrome

DAB

diaminobenzidine

GFAP

glial fibrillary acidic protein

HAD

HIV-1-associated dementia

LDH

lactate dehydrogenase

LPS

lipopolysaccharide

MAP-2

microtubule associated protein-2

MCM

monocyte-derived macrophage conditioned media

MDM

monocyte-derived macrophages

MCSF

macrophage colony stimulating factor

MP

mononuclear phagocytes

NAD+

nicotinamide adenine dinucleotide

NF

neurofilament

NGS

normal goat serum

NSE

neuronal specific enolase

RT

reverse transcriptase

TMB

3,3′,5,5′-tetramethylbenzidine

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Copyright information

© Springer 2001

Authors and Affiliations

  • Jialin Zheng
    • 1
    • 2
    Email author
  • Michael R. Thylin
    • 1
    • 2
  • Robin L. Cotter
    • 1
    • 2
  • Alicia L. Lopez
    • 1
    • 2
  • Anuja Ghorpade
    • 1
    • 2
  • Yuri Persidsky
    • 1
    • 2
  • Huangui Xiong
    • 1
    • 2
  • Gary B. Leisman
    • 1
    • 2
  • My Hanh Che
    • 1
    • 2
  • Howard E. Gendelman
    • 1
    • 2
    • 3
    • 4
  1. 1.The Center for Neurovirology and Neurodegenerative DisordersUniversity of Nebraska Medical CenterOmaha
  2. 2.The Departments of Pathology and MicrobiologyUniversity of Nebraska Medical CenterOmaha
  3. 3.Departments of MedicineUniversity of Nebraska Medical CenterOmaha
  4. 4.The Eppley Institute for Research in Cancer and Allied DiseasesUniversity of Nebraska Medical CenterOmaha

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