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-ßCH2 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 Hα 4.40-Hß 2.80 ppm) is more abundant than the extended GSH form (characteristic NMR shift signature Cys Hα 4.56-Hß 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.

In Vivo 13C Magnetic Resonance Spectroscopy for Assessing Brain Biochemistry in Health and Disease.

Magnetic resonance spectroscopy (MRS) is a non-invasive technique that contributes to the elucidation of brain biochemistry. 13C MRS enables the detection of specific neurochemicals and their neuroenergetic correlation with neuronal function. The synergistic outcome of 13C MRS and the infusion of 13C-labeled substrates provide an understanding of neurometabolism and the role of glutamate/gamma-aminobutyric acid (GABA) neurotransmission in diseases, such as Alzheimer's disease, schizophrenia, and bipolar disorder. Moreover, 13C MRS provides a window into the altered flux rate of different pathways, including the tricarboxylic acid cycle (TCA) and the glutamate/glutamine/GABA cycle, in health and in various diseases. Notably, the metabolic flux rate of the TCA cycle often decreases in neurodegenerative diseases. Additionally, 13C MRS can be used to investigate several psychiatric and neurological disorders as it directly reflects the real-time production and alterations of key brain metabolites. This review aims to highlight the chronology, the technological advancements, and the applications of 13C MRS in various brain diseases.