Distribution Pattern of Closed and Extended Forms of Glutathione in the Human Brain: MR Spectroscopic Study

Glutathione (GSH) is a potent antioxidant synthesized de novo in cells and helps to detoxify free radicals in the brain and other organs. In vitro NMR studies from various research groups have reported primarily two sets of chemical shifts (2.80 or 2.96 ppm) of Cys-βCH₂ depending on GSH sample preparation in either inert or oxygenated environments. A multi-center in vivo MRS human study has also validated the presence of two types of GSH conformer in the human brain. Our study is aimed at investigating the distribution patterns of the two GSH conformers from five brain regions, namely, ACC (anterior cingulate cortex), PCC (posterior cingulate cortex), LPC (left parietal cortex), LH (left hippocampus), and CER (cerebellum). GSH was measured using a 3T MRI scanner using MEGA-PRESS pulse sequence in healthy young male and female populations (M/F = 5/9; age 32.8 ± 5.27 years). We conclude that the closed GSH conformer (characteristic NMR shift signature: Cys H_α 4.40-H_β 2.80 ppm) is more abundant than the extended GSH form (characteristic NMR shift signature Cys H_α 4.56-H_β 2.95 ppm). Closed conformer has a non-uniform distribution (ACC < CER < LH < PCC < LPC) in the healthy brain. On the contrary, the extended form of GSH has a uniform distribution in various anatomical regions.