These authors equally contributed to the study.
An in vivo ultrahigh field 14.1 T 1H-MRS study on 6-OHDA and α-synuclein-based rat models of Parkinson's disease: GABA as an early disease marker
Article first published online: 18 JUN 2012
Copyright © 2012 John Wiley & Sons, Ltd.
NMR in Biomedicine
Volume 26, Issue 1, pages 43–50, January 2013
How to Cite
Coune, P. G., Craveiro, M., Gaugler, M. N., Mlynárik, V., Schneider, B. L., Aebischer, P. and Gruetter, R. (2013), An in vivo ultrahigh field 14.1 T 1H-MRS study on 6-OHDA and α-synuclein-based rat models of Parkinson's disease: GABA as an early disease marker. NMR Biomed., 26: 43–50. doi: 10.1002/nbm.2817
- Issue published online: 26 DEC 2012
- Article first published online: 18 JUN 2012
- Manuscript Accepted: 14 APR 2012
- Manuscript Revised: 29 FEB 2012
- Manuscript Received: 25 JUL 2011
- Parkinson's disease;
- proton magnetic resonance spectroscopy;
- rat model
The detection of Parkinson's disease (PD) in its preclinical stages prior to outright neurodegeneration is essential to the development of neuroprotective therapies and could reduce the number of misdiagnosed patients. However, early diagnosis is currently hampered by lack of reliable biomarkers. 1H magnetic resonance spectroscopy (MRS) offers a noninvasive measure of brain metabolite levels that allows the identification of such potential biomarkers. This study aimed at using MRS on an ultrahigh field 14.1 T magnet to explore the striatal metabolic changes occurring in two different rat models of the disease. Rats lesioned by the injection of 6-hydroxydopamine (6-OHDA) in the medial-forebrain bundle were used to model a complete nigrostriatal lesion while a genetic model based on the nigral injection of an adeno-associated viral (AAV) vector coding for the human α-synuclein was used to model a progressive neurodegeneration and dopaminergic neuron dysfunction, thereby replicating conditions closer to early pathological stages of PD. MRS measurements in the striatum of the 6-OHDA rats revealed significant decreases in glutamate and N-acetyl-aspartate levels and a significant increase in GABA level in the ipsilateral hemisphere compared with the contralateral one, while the αSyn overexpressing rats showed a significant increase in the GABA striatal level only. Therefore, we conclude that MRS measurements of striatal GABA levels could allow for the detection of early nigrostriatal defects prior to outright neurodegeneration and, as such, offers great potential as a sensitive biomarker of presymptomatic PD. Copyright © 2012 John Wiley & Sons, Ltd.