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.