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.
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