Combinatorial assessments of brain tissue metabolomics and histopathology in rodent models of human immunodeficiency virus infection

Adrian A. Epstein, Prabagaran Narayanasamy, Prasanta K. Dash, Robin High, Sai Praneeth R Bathena, Santhi Gorantla, Larisa Y Poluektova, Yazen Alnouti, Howard Eliot Gendelman, Michael D. Boska

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Metabolites are biomarkers for a broad range of central nervous system disorders serving as molecular drivers and byproducts of disease pathobiology. However, despite their importance, routine measures of brain tissue metabolomics are not readily available based on the requirements of rapid tissue preservation. They require preservation by microwave irradiation, rapid freezing or other methods designed to reduce post mortem metabolism. Our research on human immunodeficiency virus type one (HIV-1) infection has highlighted immediate needs to better link histology to neural metabolites. To this end, we investigated such needs in well-studied rodent models. First, the dynamics of brain metabolism during ex vivo tissue preparation was shown by proton magnetic resonance spectroscopy in normal mice. Second, tissue preservation methodologies were assessed using liquid chromatography tandem mass spectrometry and immunohistology to measure metabolites and neural antigens. Third, these methods were applied to two animal models. In the first, immunodeficient mice reconstituted with human peripheral blood lymphocytes then acutely infected with HIV-1. In the second, NOD scid IL2 receptor gamma chain knockout mice were humanized with CD34+ human hematopoietic stem cells and chronically infected with HIV-1. Replicate infected animals were treated with nanoformulated antiretroviral therapy (nanoART). Results from chronic infection showed that microgliosis was associated with increased myoinostitol, choline, phosphocholine concentrations and with decreased creatine concentrations. These changes were partially reversed with nanoART. Metabolite responses were contingent on the animal model. Taken together, these studies integrate brain metabolomics with histopathology towards uncovering putative biomarkers for neuroAIDS.

Original languageEnglish (US)
Pages (from-to)1224-1238
Number of pages15
JournalJournal of Neuroimmune Pharmacology
Volume8
Issue number5
DOIs
StatePublished - Dec 1 2013

Fingerprint

Metabolomics
Virus Diseases
Tissue Preservation
HIV-1
Rodentia
HIV
Brain
Animal Models
Biomarkers
Phosphorylcholine
Creatine
Interleukin-2 Receptors
Central Nervous System Diseases
Microwaves
Hematopoietic Stem Cells
Tandem Mass Spectrometry
Choline
Knockout Mice
Liquid Chromatography
Freezing

Keywords

  • Antigen preservation
  • Focused beam microwave irradiation
  • Human immunodeficiency virus type one
  • Magnetic resonance spectroscopy
  • Metabolomics
  • Neural antigens
  • neuroAIDS

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Combinatorial assessments of brain tissue metabolomics and histopathology in rodent models of human immunodeficiency virus infection. / Epstein, Adrian A.; Narayanasamy, Prabagaran; Dash, Prasanta K.; High, Robin; Bathena, Sai Praneeth R; Gorantla, Santhi; Poluektova, Larisa Y; Alnouti, Yazen; Gendelman, Howard Eliot; Boska, Michael D.

In: Journal of Neuroimmune Pharmacology, Vol. 8, No. 5, 01.12.2013, p. 1224-1238.

Research output: Contribution to journalArticle

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