Metabolic Changes Detected by Ex Vivo High Resolution 1H NMR Spectroscopy in the Striatum of 6-OHDA-Induced Parkinson’s Rat

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons; however, its crucial mechanism of the metabolic changes of neurotransmitters remains ambiguous. The pathological mechanism of PD might involve cerebral metabolism perturbations. In this study, ex vivo proton nuclear magnetic resonance ((1)H NMR) was used to determine the level changes of 13 metabolites in the bilateral striatum of 6-hydroxydopamine (6-OHDA)-induced PD rats. The results showed that, in the right striatum of 6-OHDA-induced PD rats, increased levels of glutamate (Glu) and γ-aminobutyric acid (GABA) concomitantly with decreased level of glutamine (Gln) were observed compared to the control. Whereas, in the left striatum of 6-OHDA-induced PD rats, increased level of Glu with decreased level of GABA and unchanged Gln were observed. Other cerebral metabolites including lactate, alanine, creatine, succinate, taurine, and glycine were also found to have some perturbations. The observed metabolic changes for Glu, Gln, and GABA are mostly likely the result of a shift in the steady-state equilibrium of the Gln-Glu-GABA metabolic cycle between astrocytes and neurons. The altered Gln and GABA levels are most likely as a strategy to protect neurons from Glu excitotoxic injury after striatal dopamine depletion. Changes in energy metabolism and tricarboxylic acid cycle might be involved in the pathogenesis of PD.

Alterations in Energy/Redox Metabolism Induced by Mitochondrial and Environmental Toxins: A Specific Role for Glucose-6-Phosphate-Dehydrogenase and the Pentose Phosphate Pathway in Paraquat Toxicity

“…However, extracellular glutamine accumulation was reduced (Figure 4E). Contradictory findings have been reported regarding the changes in levels of glutamate and glutamine in response to these neurotoxins 33,34 or in the serum and cerebrospinal fluid of PD patients. 35,36 Interestingly, despite TCA cycle blockage by paraquat, both TCA cycle metabolites oxoglutarate and succinate remained unchanged.…”

The effect of striatal dopamine depletion on striatal and cortical glutamate: A mini-review

“…One study examined the effect of bilateral 6-hydroxydopamine (6-OHDA) lesions in Sprague-Dawley rats on striatal concentrations of glutamate, glutamine, and GABA measured with 1 H-MRS ex vivo (Gao et al, 2013). Compared to controls, 6-OHDA rats showed increased concentrations of glutamate (1.63 ± 0.24 vs. 1.91 ± 0.1, p = 0.010) and GABA (0.55 ± 0.12 vs. 0.69 ± 0.05, p = 0.009) in the right striatum, as well as a decrease in glutamine (1.37 ± 0.32 vs. 1.13 ± 0.06, p = 0.049).…”

NMR Metabolomics Analysis of Parkinson's Disease

“…Untargeted metabolomics has been recently applied to PD in order to identify disease biomarkers and for the investigation of drug metabolites resulting from PD treatment [216-220]. Bogdanov et al [216] identified approximately 2000 metabolites in plasma samples obtained from 25 healthy controls and 66 PD patients by using high performance liquid chromatography coupled with electrochemical coulometric array detection (LCECA).…”

“…Gao et al [220] used 1D 1 H-NMR spectroscopy and PLS to detect metabolic changes in the striatum of 6-OHDA-induced Parkinson's rat. The right striatum of Sprague–Dawley rats were injected with 1.5 μg/μL of 6-OHDA.…”