Oxidative stress may be a hallmark of many neurodegenerative diseases and may be implicated in normal aging. Glutathione in its reduced form (GSH) is a major antioxidant in the brain and it is proposed to modulate the redox status. Recently, several biomarkers in plasma and cerebrospinal fluid that may be related to oxidative stress have been reported. To date, however, there has been no direct neurochemical marker in the living human brain as a measure of long-term ongoing changes that occur during aging and neurodegeneration. Recent advances in magnetic resonance (MR) techniques have allowed for the in vivo measurement of many neurochemicals such as N-acetyl-aspartate, choline, creatine, glutamate and glutamine in a completely non-invasive manner. However, the detection of GSH has not been in a major effort primarily due to technical challenges for reliable measurements. Hence, the development of a non-invasive and quantitative measurement of GSH would be an important and significant advance. We propose a two-dimensional multiple quantum spectroscopy method for the detection of GSH in the human brain without any contamination of signals from other metabolites. Additionally, we will validate the accuracy of GSH quantification with our proposed technique using biochemical analyses employed in parallel to our MR measurements in the rat brain. This methodology has great potential to provide a quantitative measure of oxidative stress and to provide new insights into the role of GSH in aging, and the pathogenesis and treatment of many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Small Research Grants (R03)
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Special Emphasis Panel (ZAG1-ZIJ-5 (J6))
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Wise, Bradley C
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Nathan Kline Institute for Psychiatric Research
United States
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Choi, In-Young; Lee, Phil; Adany, Peter et al. (2018) In vivo evidence of oxidative stress in brains of patients with progressive multiple sclerosis. Mult Scler 24:1029-1038
Gandal, Michael J; Haney, Jillian R; Parikshak, Neelroop N et al. (2018) Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap. Science 359:693-697
Choi, In-Young; Lee, Phil; Hughes, Abbey J et al. (2017) Longitudinal changes of cerebral glutathione (GSH) levels associated with the clinical course of disease progression in patients with secondary progressive multiple sclerosis. Mult Scler 23:956-962
Choi, In-Young; Lee, Phil (2013) Doubly selective multiple quantum chemical shift imaging and T(1) relaxation time measurement of glutathione (GSH) in the human brain in vivo. NMR Biomed 26:28-34
Choi, I-Y; Lee, S-P; Denney, D R et al. (2011) Lower levels of glutathione in the brains of secondary progressive multiple sclerosis patients measured by 1H magnetic resonance chemical shift imaging at 3 T. Mult Scler 17:289-96
Choi, In-Young; Lee, Sang-Pil; Merkle, Hellmut et al. (2006) In vivo detection of gray and white matter differences in GABA concentration in the human brain. Neuroimage 33:85-93
Choi, In-Young; Lee, Sang-Pil; Shen, Jun (2005) Selective homonuclear Hartmann-Hahn transfer method for in vivo spectral editing in the human brain. Magn Reson Med 53:503-10
Choi, In-Young; Lee, Sang-Pil; Shen, Jun (2005) In vivo single-shot three-dimensionally localized multiple quantum spectroscopy of GABA in the human brain with improved spectral selectivity. J Magn Reson 172:9-16
Choi, In-Young; Lee, Sang-Pil; Merkle, Hellmut et al. (2004) Single-shot two-echo technique for simultaneous measurement of GABA and creatine in the human brain in vivo. Magn Reson Med 51:1115-21
Choi, In-Young; Gruetter, Rolf (2004) Dynamic or inert metabolism? Turnover of N-acetyl aspartate and glutathione from D-[1-13C]glucose in the rat brain in vivo. J Neurochem 91:778-87

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