Cerebrospinal fluid proteomics reveals potential pathogenic changes in the brains of SIV-infected monkeys

Gurudutt N Pendyala, Sunia A. Trauger, Ewa Kalisiak, Ronald J. Ellis, Gary Siuzdak, Howard S Fox

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The HIV-1-associated neurocognitive disorder occurs in approximately one-third of infected individuals. It has persisted in the current era of antiretroviral therapy, and its study is complicated by the lack of biomarkers for this condition. Since the cerebrospinal fluid is the most proximal biofluid to the site of pathology, we studied the cerebrospinal fluid in a nonhuman primate model for HIV-1-associated neurocognitive disorder. Here we present a simple and efficient liquid chromatography-coupled mass spectrometry-based proteomics approach that utilizes small amounts of cerebrospinal fluid. First, we demonstrate the validity of the methodology using human cerebrospinal fluid. Next, using the simian immunodeficiency virus-infected monkey model, we show its efficacy in identifying proteins such as alpha-1-antitrypsin, complement C3, hemopexin, IgM heavy chain, and plasminogen, whose increased expression is linked to disease. Finally, we find that the increase in cerebrospinal fluid proteins is linked to increased expression of their genes in the brain parenchyma, revealing that the cerebrospinal fluid alterations identified reflect changes in the brain itself and not merely leakage of the blood-brain or blood-cerebrospinal fluid barriers. This study reveals new central nervous system alterations in lentivirus-induced neurological disease, and this technique can be applied to other systems in which limited amounts of biofluids can be obtained.

Original languageEnglish (US)
Pages (from-to)2253-2260
Number of pages8
JournalJournal of proteome research
Volume8
Issue number5
DOIs
StatePublished - May 1 2009

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Cerebrospinal fluid
Proteomics
Haplorhini
Cerebrospinal Fluid
Brain
HIV-1
Blood
Hemopexin
Cerebrospinal Fluid Proteins
Simian Immunodeficiency Virus
alpha 1-Antitrypsin
Lentivirus
Complement C3
Plasminogen
Liquid chromatography
Neurology
Biomarkers
Pathology
Viruses
Liquid Chromatography

Keywords

  • Biomarker
  • CSF
  • Dementia
  • HIV
  • Monkey
  • Neuropathology
  • Proteomics
  • SIV

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Cerebrospinal fluid proteomics reveals potential pathogenic changes in the brains of SIV-infected monkeys. / Pendyala, Gurudutt N; Trauger, Sunia A.; Kalisiak, Ewa; Ellis, Ronald J.; Siuzdak, Gary; Fox, Howard S.

In: Journal of proteome research, Vol. 8, No. 5, 01.05.2009, p. 2253-2260.

Research output: Contribution to journalArticle

Pendyala, Gurudutt N ; Trauger, Sunia A. ; Kalisiak, Ewa ; Ellis, Ronald J. ; Siuzdak, Gary ; Fox, Howard S. / Cerebrospinal fluid proteomics reveals potential pathogenic changes in the brains of SIV-infected monkeys. In: Journal of proteome research. 2009 ; Vol. 8, No. 5. pp. 2253-2260.
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