NMR-Based Metabolomics Reveal a Recovery from Metabolic Changes in the Striatum of 6-OHDA-Induced Rats Treated with...

Basic fibroblast growth factor (bFGF) has a potential role in the treatment of Parkinson's disease (PD) due to its neurotrophic effect on dopaminergic neurons. To address the metabolic mechanisms of bFGF administration on PD, we have analyzed the metabolic profiles in the striatum of 6-hydroxydopamine (6-OHDA)-induced PD rats after the treatment with bFGF using ¹H NMR spectroscopy and partial least squares-discriminant analysis (PLS-DA). In the present study, we found that bFGF treatment can effectively recover PD-induced loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. Metabolomic analyses reveal that PLS-DA failed to discriminate between the control and bFGF groups, indicating that the metabolic difference between these two groups was negligible. However, reliable PLS-DA models can be developed between control and PD groups as well as between PD and bFGF groups, which is attributed to changes in a series of metabolites including GABA, glutamate (Glu), glutamine (Gln), lactate, N-acetylaspartate, creatine, taurine, and myo-inositol. ANOVA results show that the levels of all these metabolites were significantly increased in PD rats relative to normal rats, while PD-induced increase can be significantly reduced to normal levels after bFGF administration. In conclusion, our results suggest that a recovery from PD-induced metabolic disorders may be achieved by bFGF treatment, involving Gln/Glu-GABA cycle, energy metabolism, osmoregulation, and inflammation.