Measurement of Glutamate Suppression in a 6-OHDA-Induced Dopamine Deficiency Rat Model Following Acute Single-Dose L-DOPA Using GluCEST/MRS

<b>Background/Objectives</b>: The Glutamate Chemical Exchange Saturation Transfer (GluCEST) technique is an advanced imaging modality that enables non-invasive glutamate quantification using MRI. <b>Methods</b>: This study evaluated glutamate dynamics in Parkinson's disease (PD) using a unilateral PD rat model, in which Wistar rats received 6-hydroxydopamine (6-OHDA) injections into the medial forebrain bundle, selectively eliminating dopaminergic neurons in the substantia nigra-striatum pathway. <b>Results</b>: The PD rat model exhibited a significant GluCEST increase (MTR Values: 3.0 ppm) compared to the sham-operated group, which was suppressed by administration of L-DOPA, a dopamine precursor drug (Sham: 0.9 ± 0.4%, PD: 2.0 ± 0.2%, Sham L-DOPA: 0.9 ± 0.5%, PD_L-DOPA: 0.8 ± 0.7%, <i>p</i> < 0.01). Additionally, magnetic resonance spectroscopy-derived glutamate data were consistent with GluCEST findings (Sham: 1.4 ± 0.03, PD: 1.7 ± 0.06, Sham_L-DOPA: 1.4 ± 0.12, PD_L-DOPA: 1.4 ± 0.10, <i>p</i> < 0.01). <b>Conclusions</b>: These findings suggest that GluCEST and magnetic resonance spectroscopy are valuable for assessing abnormal glutamate dynamics in the 6-OHDA-induced rat PD model. Furthermore, GluCEST may detect suppressed glutamate secretion following L-DOPA treatment, underscoring its potential for monitoring disease progression and therapeutic responses in PD.