4.4 Article

Factor analysis reveals differences in brain metabolism in macaques with SIV/AIDS and those with SIV-induced encephalitis

Journal

NMR IN BIOMEDICINE
Volume 21, Issue 8, Pages 878-887

Publisher

WILEY
DOI: 10.1002/nbm.1276

Keywords

human immunodeficiency virus (HIV); simian immunodeficiency virus (SIV); MRS; N-acetylaspartate; creatine; encephalitis; frontal cortex; factor analysis

Funding

  1. NCRR NIH HHS [RR00168-39, K01 RR000150, P41 RR014075, P41 RR14075, K26 RR000168, RR000150, RR13213, P51 RR000168] Funding Source: Medline
  2. NIBIB NIH HHS [P41 EB002026, EB002026] Funding Source: Medline
  3. NINDS NIH HHS [K25 NS051129, R01 NS034626, NS050041, R01 NS050041, NS051129, NS34626, K25 NS051129-04] Funding Source: Medline

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MRS has often been used to study metabolic processes in the HIV-infected brain. However, it remains unclear how changes in individual metabolites are related to one another in this context of virus-induced central nervous system dysfunction. We used factor analysis (FA) to identify patterns of metabolite distributions from an MRS study of healthy macaques and those infected with simian immunodeficiency virus (SIV) which were moribund with AIDS. FA Summarized the correlations from nine metabolites into three main factors. Factor 3 identified patterns that discern healthy animals from those with SIV/AIDS. Factor 2 was able to differentiate between animals that had encephalitis and those moribund with AIDS but lacking encephalitis. Specifically Factor 2 was able to distinguish animals with moderate to severe encephalitis from animals with mild or no encephalitis as well as uninfected controls. FA not only confirmed the involvement of neuronal metabolites (N-acetylaspartate and glutamate) in disease severity, but also detected changes in creatine myo-inositol that have not been observed in the SIV macaque model previously. These results suggest that the divergent pathways of N-acetylaspartate and creatine in this disease may enable the commonly reported ratio N-acetylaspartate/creatnine to be a more sensitive marker of disease severity. Copyright (C) 2008 John Wiley & Sons. Ltd.

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