Elevated homocarnosine and GABA in subject on isoniazid as assessed through 1H MRS at 7T

• Published in: Analytical biochemistry Vol. 599; p. 113738
• Main Authors: Landheer, Karl, Prinsen, Hetty, Petroff, Ognen A., Rothman, Douglas L., Juchem, Christoph
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.06.2020
• Subjects: 7 T; Adult; brain; Brain Chemistry; Carnosine - analogs & derivatives; Carnosine - analysis; creatine; Female; GABA; gamma-aminobutyric acid; gamma-Aminobutyric Acid - analysis; Healthy Volunteers; Homocarnosine; Humans; Isoniazid; Isoniazid - administration & dosage; Magnetic Resonance Spectroscopy; magnetism; Male; metabolites; Middle Aged; spectroscopy; Young Adult; Magnetic resonance spectroscopy; GABA; 7 T; Isoniazid; Homocarnosine
• ISSN: 0003-2697; 1096-0309; 1096-0309
• DOI: 10.1016/j.ab.2020.113738

Typical magnetic resonance spectroscopy J-editing methods designed to quantify GABA suffer from contamination of both overlapping macromolecules and homocarnosine signal, introducing potential confounds. The aim of this study was to develop a novel method to assess accurately both the relative concentrations of homocarnosine as well as GABA free from overlapping creatine, homocarnosine and macromolecule signal. A novel method which utilized the combination of echo time STEAM and MEGA-sLASER magnetic resonance spectroscopy experiments at 7T were used to quantify the concentration of GABA and homocarnsoine independently, which are typically quantified in tandem. The metabolites GABA and homocarnosine were measured in brain of 6 healthy control subjects, and in a single subject medicated with isoniazid. It was found that (16.6±10.2)% of the supposed GABA signal in the brain originated from homocarnosine, and that isoniazid caused significantly elevated concentration of GABA and homocarnosine in a single subject compared to controls. A novel method to accurately assess both the relative concentrations of homocarnosine and GABA free from overlapping creatine, homocarnosine and macromolecule signal at 7T was developed. The metabolites GABA and homocarnosine, were measured in 6 healthy control subjects, and in a single medicated subject who demonstrated elevated GABA and homocarnosine. [Display omitted] •Novel method developed to measure concentration of GABA and homocarnosine.•Found that (16.6±10.2)% of the GABA signal originated from homocarnosine.•Isoniazid caused significantly elevated concentration of GABA and homocarnosine.