1H NMR-Based Metabolomics Reveals Metabolic Changes in the Hippocampus of MPTP-induced Mice

Cognitive impairment is a crucial non-motor symptom in patients with Parkinson’s disease (PD). Research carried out in recent years has indicated an association between hippocampus and cognitive deficits in PD patients with or without dementia. However, the molecular mechanism is still unclear. Metabolites including neurotransmitters modulated lots of biological functions in central nervous system. The influence of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which could lead to Parkinsonism in non-human primate and mice, on hippocampal metabolites is still unclear. In this study, HE staining and ¹H NMR were used to assess the neuronal morphology and metabolite levels in the hippocampus of MPTP-injected mice on the 1, 7, 21, and 35. Our data revealed that MPTP cannot result in any influence on the neuronal morphology in the hippocampus of mice injected with MPTP. Concentrations of Lactate (Lac), Alanine (Ala), Glutamate (Glu), Glycine (Gly), Creatine (Cr), Taurine (Tau), Choline (Cho) and Phosphocholine (P-Cho) were detected in the hippocampus using ¹H NMR. On the day 1, increases of all these metabolite levels were induced by MPTP-treatment, and concentrations of Lac, Cr, Glu, Cho, and P-Cho were increased in the hippocampus in the day 7. However, only P-Cho level was boosted in the hippocampus of MPTP-injected mice in the day 21. At last, a higher level of Cr was detected in the MPTP group in the day 35. Our results indicated that metabolic changes appeared in the day 1 after the last injection of MPTP prior to other symptoms of rodent model. These data suggested that metabolic dysfunction might be a good marker for the diagnosis of PD.