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Abstract #1055

1H MRS and Tandem Mass Spectrometric Metabolite Signatures Herald HIV-1 Induced Metabolic Abnormalities in the Brains of Humanized Mice

Michael Douglas Boska1, Adrian A. Epstein2, Prasanta K. Dash2, Nathan A. Smith2, Prabagaran Narayanasamy2, Harris A. Gelbard3, Larisa Y. Poluektova2, Howard E. Gendelman2

1Radiology, University of Nebraska Medical Center, Omaha, NE, United States; 2Pharmacology and Experimental Neurosciences, University of Nebraska Medical Center, Omaha, NE, United States; 3Neurology/Center for Neural Development and Disease, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States

Immunodeficient mice engrafted with human stem cells develop a functional human immune system. After infection with human immunodeficiency virus type one (HIV-1) these mice develop an encephalopathy reflective of human disease. The brain metabolome was elucidated at four week intervals by volume localized 1H MRS or at study end by ultraperformance liquid chromatography tandem mass spectrometry. NAA, creatine, choline brain levels were altered and changes were congruent for all methods. MRS-detected brain metabolites predicted brain pathologies in HIV-1 infected humanized mice. The studies are of translational value in predicting disease course or response to therapy in an infected human host.