• Journal of Korean Neurosurgical Society
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• v.29 no.2
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• pp.155-166
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• 2000

This study was designed to investigate the underlying mechanisms for the temporal changes of the striatal dopamine D2 receptors in the rat model of parkinsonism. After injection of the 6-hydroxydopamine into the substantia nigra of adult rats, we measured the receptor binding capacity(Bmax), mRNA and protein of the D2 receptor at 2, 4 and 8 weeks. Following the lesion, mRNA and protein were elevated simultaneously on both sides of the striata. They showed more increase on the normal side at 2 and 4 weeks, and then they were almost equally abundant on both sides at 8 weeks. We also observed their increased production in the diffuse cortical and subcortical regions. The Bmax value also increased bilaterally in both striata, and was higher on the normal side at 2 weeks and then on the lesioned side at 4 and 8 weeks. These findings suggest that production of the striatal D2 receptor is regulated at the transcriptional level in this animal model. They also imply that this control may be mediated through a pathway which can have influence on the whole brain, rather than the local control of the dopamine content alone. The measured functional activity(Bmax) of the D2 receptor was not proportional to the amount of the receptor mRNA and proteins produced. This difference may be explained by the post-translational modification of the receptor proteins, which may be controlled by such factor as the local concentration of dopamine.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.4
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• pp.272-279
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• 2007

Purpose: The aim of this study was to evaluate the discriminating nature of $^{123}I-FP-CIT$ SPECT in patients with parkinsonism. Methods: $^{123}I-FP-CIT$ SPECT images acquired from the 18 normal controls; NC ($60.4{\pm}10.0$ yr) and 237 patients with parkinsonism ($65.9{\pm}9.2$ yr) were analyzed. From spatialIy normalized images, regional counts of the caudate, putamen, and occipital lobe were obtained using region of interest method. Binding potential (BP) was calculated with the ratio of specific to nonspecific binding activity at equilibrium. Additionally, the BP ratio of putamen to caudate (PCR) and asymmetric Index (ASI) were measured. Results: BPs of NC $3.37{\pm}0.57,\; 3.10{\pm}0.41,\; 3.23{\pm}0.48$ for caudate, putamen, whole striatum, respectively) had no significant difference with those of essential tremor; ET ($3.31{\pm}0.64,\; 3.06{\pm}0.61,\; 3.14{\pm}0.63$) and Alzheimer's disease; AD (3.33 $\pm$0.60, 3.29$\pm$0.79, 3.31$\pm$0.70), but were higher than those of Parkinson's disease; PD (1.92$\pm$0.74, 1.39$\pm$0.68, 1.64$\pm$0.68), multiple system atrophy; MSA (2.36$\pm$1.07, 2.16$\pm$0.91, 2.26$\pm$0.96), and dementia with Lewy body; DLB (1.95$\pm$0.72, 1.64$\pm$0.65, 1.79$\pm$0.66)(p<0.005). PD had statisticalIy lower values of PER and higher values of ASI than those of NC (p<0.005). And PD had significantIy lower value of PCR, higher ASI and lower BP in the putamen and whole striatum than MSA (p<0.05). Conclusion: Dopamine transporter image of $^{123}I-FP-CIT$ SPECT was a good value in differential diagnosis of parkinsonism.

• Korean Journal of Radiology
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• v.25 no.3
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• pp.267-276
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• 2024

Objective: To evaluate the diagnostic performance of susceptibility map-weighted imaging (SMwI) taken in different acquisition planes for discriminating patients with neurodegenerative parkinsonism from those without. Materials and Methods: This retrospective, observational, single-institution study enrolled consecutive patients who visited movement disorder clinics and underwent brain MRI and ¹⁸F-FP-CIT PET between September 2021 and December 2021. SMwI images were acquired in both the oblique (perpendicular to the midbrain) and the anterior commissure-posterior commissure (AC-PC) planes. Hyperintensity in the substantia nigra was determined by two neuroradiologists. ¹⁸F-FP-CIT PET was used as the reference standard. Inter-rater agreement was assessed using Cohen;s kappa coefficient. The diagnostic performance of SMwI in the two planes was analyzed separately for the right and left substantia nigra. Multivariable logistic regression analysis with generalized estimating equations was applied to compare the diagnostic performance of the two planes. Results: In total, 194 patients were included, of whom 105 and 103 had positive results on ¹⁸F-FP-CIT PET in the left and right substantia nigra, respectively. Good inter-rater agreement in the oblique (κ = 0.772/0.658 for left/right) and AC-PC planes (0.730/0.741 for left/right) was confirmed. The pooled sensitivities for two readers were 86.4% (178/206, left) and 83.3% (175/210, right) in the oblique plane and 87.4% (180/206, left) and 87.6% (184/210, right) in the AC-PC plane. The pooled specificities for two readers were 83.5% (152/182, left) and 82.0% (146/178, right) in the oblique plane, and 83.5% (152/182, left) and 86.0% (153/178, right) in the AC-PC plane. There were no significant differences in the diagnostic performance between the two planes (P > 0.05). Conclusion: There are no significant difference in the diagnostic performance of SMwI performed in the oblique and AC-PC plane in discriminating patients with parkinsonism from those without. This finding affirms that each institution may choose the imaging plane for SMwI according to their clinical settings.

• Annals of Clinical Neurophysiology
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• v.8 no.2
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• pp.107-124
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• 2006

The basal ganglia are a group of nuclei located in the deep portion of the brain. Along with the cerebellum, the basal ganglia have a major role in controlling human voluntary movements, and their dysfunction is apparently responsible for various involuntary movements. Although the exact mechanism of how the basal ganglia control movements has yet to be clarified, the model of focused selection (through the direct pathway) and tonic inhibition (via the indirect pathway) is proposed to be a principal functional model of the basal ganglia. Parkinson's disease (PD) is classically characterized by bradykinesia, rigidity and tremor-at-rest. All features seem to be associated with dopamine depletion resulting from the degeneration of the nigrostriatal pathway, which produces reduced activity of the direct pathway and a concurrent enhancement of excitatory output from STN. This change may result in increased tonic background inhibition and reduced focused selection via the direct pathway, causing difficulties in performing voluntary movements selectively. However, it has not been possible to define a single underlying pathophysiologic mechanism that explains all parkinsonian symptoms. Here the data that give separate understanding to each of the three classic features are discussed.

• Animal cells and systems
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• v.16 no.1
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• pp.20-26
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• 2012

Drug-induced parkinsonism has been associated with an increased risk for Parkinson's disease. Antipsychotic drugs have long been known to cause parkinsonian symptoms. However, it remains unclear whether antipsychotics can directly damage the nigrostriatal pathway. In the present study, we investigated the toxicity mechanism of two typical antipsychotics, perphenazine and trifluoperazine, in a human dopaminergic cell line, SH-SY5Y. Perphenazine and trifluoperazine induced mitochondrial damage as evidenced by fragmentation of mitochondria, activation of Bax, cytochrome c release and a decrease in cellular ATP level. In addition, activation of caspase-3 and apoptotic nuclei were observed following the drug treatment. However, pan-caspase inhibitor did not suppress the cell death induced by the antipsychotics, suggesting that the initiated apoptosis was possibly shifted to necrosis upon caspase inhibition. Damaged mitochondria may have induced oxidative stress since the drug-induced cell death was partially suppressed by an antioxidant. Taken together, our results suggest that perphenazine and trifluoperazine can induce apoptotic cell death in a dopaminergic cell line via mitochondrial damage accompanied by oxidative stress.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.2
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• pp.150-157
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• 2020

The protective effects of a Celastrus orbiculatus Thunb (CO) extract against manganese dioxide (MnO₂)-induced cytotoxicity in cultured C6 glioma cells were examined. This study assessed the antioxidative effects, including the suppressive ability of lipid peroxidation (LP), the inhibitory ability of xanthine oxidase (XO), and the cell viability. MnO₂ decreased the cell viability remarkably in a dose-dependent manner. The XTT₅₀ value was determined to be 146.7 μM in these cultures. The cytotoxicity of MnO₂ was calculated to be mid-toxic using Borenfreund and Puerner's toxic criteria. Kaempferol (KAE) increased the cell viability damaged by MnO₂-induced cytotoxicity significantly. Regarding the protective effects of the CO extract on MnO₂-induced cytotoxicity, the CO extract increased cell viability significantly compared to the MnO₂-treated group. The CO extract also had inhibitory abilities against lipid peroxidation (LP) and xanthine oxidase (XO). From these findings, oxidative stress is involved in the cytotoxicity of MnO₂. The CO extract effectively blocked the cytotoxicity induced by MnO₂ via its antioxidative effects. Conclusively, natural resources, such as the CO extract, might be a useful agent for the diminution or improvement of the heavy metal cytotoxicity correlated with disease through oxidative stress, such as MnO₂, a Parkinsonism inducer.

• The Journal of Internal Korean Medicine
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• v.40 no.5
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• pp.743-751
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• 2019

This case report suggests the potential effects of Korean medicine for the gait disturbance and posture instability of Multiple System Atrophy-Parkinsonism (MSA-P). A patient with MSA-P who had gait disturbance and posture instability was given a series of Korean medicine, including acupuncture, pharmacopuncture, electro-acupuncture, moxibustion, and herbal medicine, for 15 days of hospitalization. During the hospitalization period, the severity and progression of the disease was measured with the Unified Multiple System Atrophy Rating Scale (UMSARS) and a video recording of a 20-meter round timed walking test. The UMSARS Part I and II scores decreased from 14 to 5 and 9 to 5, respectively. An improvement was also noted in standing and walking posture, and the walking time was shortened from 30 to 25 seconds in the 20-meter round-trip walking test. Dysarthria, dysphagia, and non-motoring symptoms like sleep behavioral disorders and constipation were also improved. The findings of this case study suggest that this series of Korean medicine has potential therapeutic effects for patients with MSA-P with motor and non-motor symptoms.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.124-124
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• 2001

Tetrahydropapaveroline(THP), a dopamine-derived 6,7-dihydroxy-l-(3',4'-dihydroxybenzyl)-1,2,3,4-tetrahydrosioquinoline, has been suspected as a possible dopaminergic neurotoxin to elicit Parkinsonism. Autoxidation or monoamine oxidase-mediated oxidation of THP and subsequent generation of reactive oxygen species (ROS) may contribute to the degeneration of dopaminergic neurons induced by this isoquinoline alkaloid.(omitted)

• Journal of Korean Neurosurgical Society
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• v.40 no.3
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• pp.196-198
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• 2006

Familial idiopathic basal ganglia calcification[FIBGC] is an inheritable neurological condition characterized by calcium deposits in the basal ganglia and extra-basal ganglia areas. The condition manifests as parkinsonism and other variable neuropsychiatric symptoms. FIBGC is a rare condition, and its pathophysiology has not yet been fully elucidated. Here we report the results of a clinical study of two related patients diagnosed with FIBGC.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.114-114
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• 2001

Tetrahydropapaveroline (THP), a dopamine-derived 6, 7-dihydroxy-1-(3' ,4'-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline, has been suspected as a possible dopaminergic neurotoxin to elicit Parkinsonism. Autooxidation or enzymatic oxidation of THP and subsequent generation of reactive oxygen species (ROS) may contribute to the degeneration of dopaminergic neurons induced by this isoquinoline alkaloid.(omitted)