In vivo detection of metabolic changes in the striatum of proteasomal inhibition-induced Parkinson’s disease in rats using proton MR spectroscopy at 9.4 T

Abstract

Purpose: Parkinson’s disease is a progressive disorder. To investigate the biochemical alterations in the striatum of rats with different stages of Parkinson’s disease induced by proteasomal inhibition, we quantified neurochemical profiles of the striatum using proton magnetic resonance spectroscopyusing 9.4 T ultra-high field imaging.

Methods: In this study, 10 μg/2 μl lactacystin, a selective proteasome inhibitor, was unilaterally injected stereotaxically into the left substantia nigra pars compacta of rats. An equal volume of saline was injected into the same region and side in the control group. Changes in motor behaviour were observed. The morphological changes of tyrosine hydroxylase-positive cells in substantia nigra pars compacta were visualized using immunohistochemistry. Tyrosine hydroxylase-positive nerve fibers were quantified. Alterations of N-acetylaspartate, choline, creatine, taurine in the different stages of Parkinson’s disease rats were detected using proton magnetic resonance spectroscopy.

Results: Application of in vivo ¹H magnetic resonance spectroscopy was repeated in both the six Parkinson’s disease rats and the six control rats across three time points during the first, second and fourth weekend after administration. In Parkinson’s disease rats, increased N-acetylaspartate and decreased taurine concentrations were observed in the left striatum at the first week after administration. The increased N-acetylaspartate and choline concentrations were observed at the second weekend. At the fourth weekend, increased creatine concentrations in the left side were observed, while other metabolites were not significantly changed.

Conclusions: Neurochemical alterations occurred in the striatum during different stages of the Parkinson’s disease model in rats. Also, 9.4 T ¹H magnetic resonance spectroscopy may be a useful tool for elucidating the progression of Parkinson’s disease through the variation of these metabolites.

Keywords:

• Parkinson’s disease
• striatum
• proteasomal inhibition
• high field MRI

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by a Science and Technology Project grant from Anhui Province, China (No. 1606c08235).