Evolution of the neurochemical profiles in the G93A-SOD1 mouse model of amyotrophic lateral sclerosis

• Published in: Journal of cerebral blood flow and metabolism 2019-07, Vol.39 (7), p.1283-1298
• Main Authors: Lei, Hongxia, Dirren, Elisabeth, Poitry-Yamate, Carole, Schneider, Bernard L, Gruetter, Rolf, Aebischer, Patrick
• Format: Article
• Language: English
• Subjects: Amyotrophic Lateral Sclerosis - enzymology; Amyotrophic Lateral Sclerosis - metabolism; Animals; Ascorbic Acid - analysis; Aspartic Acid - analogs & derivatives; Aspartic Acid - analysis; Brain - metabolism; Brain Chemistry - physiology; Brain Stem - chemistry; Corpus Striatum - chemistry; Disease Models, Animal; Disease Progression; gamma-Aminobutyric Acid - analysis; Glutamic Acid - analysis; Glutamine - analysis; Humans; Lactic Acid - analysis; Magnetic Resonance Spectroscopy; Mice; Mice, Transgenic; Motor Cortex - chemistry; Mutation; Original; Superoxide Dismutase - genetics
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1177/0271678X18756499

In vivo 1H magnetic resonance spectroscopy (1H-MRS) investigations of amyotrophic lateral sclerosis (ALS) mouse brain may provide neurochemical profiles and alterations in association with ALS disease progression. We aimed to longitudinally follow neurochemical evolutions of striatum, brainstem and motor cortex of mice transgenic for G93A mutant human superoxide dismutase type-1 (G93A-SOD1), an ALS model. Region-specific neurochemical alterations were detected in asymptomatic G93A-SOD1 mice, particularly in lactate (−19%) and glutamate (+8%) of brainstem, along with γ-amino-butyric acid (−30%), N-acetyl-aspartate (−5%) and ascorbate (+51%) of motor cortex. With disease progression towards the end-stage, increased numbers of metabolic changes of G93A-SOD1 mice were observed (e.g. glutamine levels increased in the brainstem (>+66%) and motor cortex (>+54%)). Through ALS disease progression, an overall increase of glutamine/glutamate in G93A-SOD1 mice was observed in the striatum (p