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

Molecular Neurobiology - Tập 47 - Trang 123-130 - 2012
Hong-Chang Gao1, Huan Zhu1, Cai-Yong Song1, Li Lin1, Yun Xiang2, Zhi-Han Yan3, Guang-Hui Bai3, Fa-Qing Ye1, Xiao-Kun Li1
1School of Pharmacy, Wenzhou Medical College, Wenzhou, People’s Republic of China
2Wuhan Medical and Health Center for Women and Children, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
3Radiology Department of the Second Affliated Hospital, Wenzhou Medical College, Wenzhou, People’s Republic of China

Tóm tắt

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 (1H 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.

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