(1)H NMR-based metabolomics study on a goldfish model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

• Published in: Chemico-biological interactions 2014-11, Vol.223, p.18-26
• Main Authors: Lu, Zhaoguang, Wang, Junsong, Li, Minghui, Liu, Qingwang, Wei, Dandan, Yang, Minghua, Kong, Lingyi
• Format: Article
• Language: English
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - administration & dosage; 3,4-Dihydroxyphenylacetic Acid - metabolism; Animals; Behavior, Animal - drug effects; Brain - drug effects; Brain - metabolism; Disease Models, Animal; Dopamine - metabolism; Goldfish; Humans; Lipid Metabolism - drug effects; Magnetic Resonance Spectroscopy; Metabolomics; MPTP Poisoning - complications; Parkinson Disease - etiology; Parkinson Disease - metabolism; Parkinson Disease - physiopathology; Swimming
• ISSN: 1872-7786
• DOI: 10.1016/j.cbi.2014.09.006

A goldfish (Carassius auratus) model of Parkinson's disease (PD) was constructed by a single dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) according to previously reported methods. Global metabolite changes in brain of the MPTP induced goldfish model of PD were investigated. (1)H NMR-based metabolomics combined with various statistical methods such as orthogonal partial least squares discriminant analysis (OPLS-DA) and two-dimensional statistical total correlation spectroscopy (2D-STOCSY) found significant increase of leucine, isoleucine, valine, alanine, alanylalanine, creatinine, myo-inositol, 18:2 fatty acid, total fatty acids, arachic alcohol, taurine and significant decrease of N-acetylaspartate, (phospho)creatine, (phospho)choline, betaine, glutamine, 3-hexenedioate, acetamide, malonate, isocitrate, scyllo-inositol, phosphatidylcholines, cholesterols, n-3 fatty acids, polyunsaturated fatty acids (PUFAs) in brain of MPTP induced PD goldfish. These disturbed metabolite levels were involved in oxidative stress, energy failure, neuronal cell injury and death, consistent with those observed in clinical PD patients, and rodents and primates model of PD, indicating that the acute MPTP model of goldfish was an ideal and valuable model for PD research. In addition, several unusual metabolites in brain were significantly changed between MPTP induced PD and control goldfish, which might also play an important role in the pathogenesis of PD. This study also demonstrated the applicability and potential of (1)H NMR-based metabolomics approach for evaluation of animal models of disease induced by chemicals, such as MPTP-induced PD goldfish.