Assessment of metabolic changes in the striatum of a rat model of parkinsonism: an in vivo¹H MRS study

Abstract

Degeneration of the dopaminergic neurons of the substantia nigra pars compacta in Parkinson's disease induces an abnormal activation of the glutamatergic neurotransmission system within the basal ganglia network and related structures. The aim of this study was to use proton MRS to show metabolic changes in the striatum of 6-hydroxydopamine-lesioned rats, a rodent animal model of Parkinson's disease. Animals were examined before and after extensive lesioning of the nigral dopaminergic neurons and after acute administration of L-3,4-dihydroxyphenylalanine. No significant alterations in glutamate concentrations, assessed by the MR signal dominated by glutamate with minor contributions from glutamine and g-aminobutyric acid, could be measured. The total choline/total creatine ratio was found to be reduced in the striatum of the ipsilateral hemisphere.

Morphological and Metabolic Changes in the Nigro-Striatal Pathway of Synthetic Proteasome Inhibitor (PSI)-Treated Rats: A MRI and MRS Study

“…In particular, in accordance with previous studies on humans [31] or on different animal models of PD [32], [33], we found a reduction of NAA/tCr. NAA is synthesized in the neuronal mitochondria and transported along axons and its concentration is reduced in case of neuronal loss [34], [35].…”

Assessment of metabolic changes in the striatum of a MPTP-intoxicated canine model: in vivo 1H-MRS study of an animal model for Parkinson's disease

“…Chassain et al reported a significant increase in Glu synthesis in the striatum of the rat after unilateral lesion of the dopaminergic nigrostriatal pathway using 13 C NMR spectroscopy [53]. However, another rat model of parkinsonism showed no significant change in Glx/tCr in the ipsi-dorsolateral striatum after 6-hydroxydopamine (6-OHDA) lesioning [28]. The discrepancies may be caused by the different dosage of 6-OHDA and different MRS methodology used.…”

“…To our knowledge, few in vivo 1 H-MRS studies have assessed the metabolic alterations in the canine MPTP model while most of the animal model studies for Parkinsonism induced by neurotoxin substrates were focused in small vertebrate animals like mice or rat [28][29][30][31][39][40][41].…”

“…3, we were not able to observe any difference in the Glx level in the striatum. The increase in Glu level in the striatum of MPTP-lesioned mice may be interpreted as a change in fluxes of 13 C label into and/or out of the Glu pool rather than an increase in intracellular Glu concentrations [28].…”

“…1 H-MRS has been widely used to study the metabolism of relevant brain regions for PD such as the basal ganglia [19][20][21][22][23], motor cortex [22,24], temporoparietal cortex [21,25], posterior cingulate gyrus [26] and occipital lobe [27]. In addition, a number of spectroscopic studies of rodent [28][29][30][31] and/or non-human primate model [32] for PD have been reported. The nonhuman primate model is preferable over rodents as these animals show clear and lasting behavioral features after MPTP treatment, which reflect many aspects of human PD symptoms [33].…”