NMR metabolomic of frontal cortex extracts : First study comparing two neurodegenerative diseases, Alzheimer disease and amyotrophic lateral sclerosis

Métabolomique par RMN d’extraits de cortex frontal : première étude comparant deux maladies neurodégénératives, la maladie d’Alzheimer et la sclérose latérale amyotrophique

E.P Botosoa (1) , M. Zhu (1) , C. Marbeuf-Gueye , M.N. Triba , F. Dutheil (2) , C. Duyckäerts (3) , P. Beaune (2) , M.A. Loriot (2) , L. Le Moyec (4)

1 CSPBAT - Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques
2 RTMG - Régulation de la transcription et maladies génétiques
3 Neurologie et thérapeutique expérimentale
4 UBIAE - Unité de biologie intégrative des adaptations à l'exercice

Objective This study was designed to assess the brain metabolites' variability between two neurodegenerative diseases in frontal cortex samples obtained post-mortem. NMR metabolomics was used for the first time in this context. Materials and methods 1H NMR metabolomic was applied to tissue extracts from patients with Alzheimer disease (ALZ) and patients with amyotrophic lateral sclerosis (ALS) to investigate qualitative and quantitative variations of brain metabolites. Results The Alzheimer disease metabolic signature was characterized by a high concentration of alanine, acetate, glutamate and glutamine, and low concentrations of lactate and creatine, while the ALS metabolic signature appears to be marked by high concentrations of lactate, N-acetyl aspartate, creatine, choline and myo-inositol. Moreover, in vitro 1H NMR could detect metabolites such as 3-hydroxybutyrate, alanine, succinate and aspartate that cannot be detected with in vivo NMR. Discussion The neurodegenerative diseases exhibit diverging metabolic pathways. Some of the metabolites responsible for the discrimination between the two diseases were detected before in vivo. However, this in vitro metabolomic investigation demonstrates the involvement of metabolites not detected with in vivo studies. Conclusion Upon these findings, in vitro metabolomics appears to be an efficient tool to investigate the fundamentals of the metabolic pathway modulations in these neurodegenerative diseases to help the interpretation of clinical data obtained with in vivo NMR spectroscopy. © 2012 Elsevier Masson SAS.

Keywords: 3 hydroxybutyric acid; acetic acid; alanine; choline; creatine; glutamic acid; glutamine; inositol; lactic acid; n acetylaspartic acid; succinic acid; Alzheimer disease; amyotrophic lateral sclerosis; article; autopsy; brain level; frontal cortex; human; human tissue; in vitro study; in vivo study; metabolomics; proton nuclear magnetic resonance; qualitative analysis; quantitative analysis

Domains: Life Sciences [q-bio]

E.P Botosoa, M. Zhu, C. Marbeuf-Gueye, M.N. Triba, F. Dutheil, et al.. NMR metabolomic of frontal cortex extracts : First study comparing two neurodegenerative diseases, Alzheimer disease and amyotrophic lateral sclerosis. Innovation and Research in BioMedical engineering, 2012, 33 (5-6), pp.281-286. ⟨10.1016/j.irbm.2012.08.002⟩. ⟨hal-02489961⟩