• The Korean Journal of Pain
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• v.33 no.1
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• pp.90-96
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• 2020

Background: Parkinson's disease (PD) is a neurodegenerative disorder that is the second most common disorder after Alzheimer's disease. PD includes both "motor" and "non-motor" symptoms, one of which is pain. The aim of this study was to investigate the clinical characteristics of pain in patients with PD. Methods: This cross-sectional study included 250 patients diagnosed with PD, 70% of which had mild to moderate PD (stages 2/3 of Hoehn and Yahr scale). The average age was 67.4 years, and the average duration since PD diagnosis was 7.1 years. Relevant data collected from PD patients were obtained from their personal medical history. Results: The prevalence of pain was found to be high (82%), with most patients (79.2%) relating their pain to PD. Disease duration was correlated with the frequency of intense pain (R: 0.393; P < 0.05). PD pain is most frequently perceived as an electrical current (64%), and two pain varieties were most prevalent (2.60 ± 0.63). Our findings confirm links between pain, its evolution over time, its multi-modal character, the wide variety of symptoms of PD, and the female sex. Conclusions: Our results demonstrated that the pain felt by PD patients is mainly felt as an electrical current, which contrasts with other studies where the pain is described as burning and itching. Our classification is innovative because it is based on anatomy, whereas those of other authors were based on syndromes.

• Korean Journal of Oriental Medicine
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• v.15 no.3
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• pp.53-61
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• 2009

Oxytocin(OT), classically known to stimulate labour and milk ejection, contributes to play an important role in a wide range of behavioral effects including drug addiction. An increasing body of evidence suggests that OT ameliorates acute and long-term effects of commonly used drugs by means of interacting with the mesolimbic dopamine system. Mesolimbic dopamine system is thought to play a major role in the reinforcing properties of drug abuse. Oxytocin receptors in the nucleus accumbens(NAc) and ventral tegmental area(VTA) have been implicated in the regulation of reinforcing effects in abused drugs. In the same way acupuncture may attenuate the reinforcing effects of abused drugs in the NAc and VTA. We have an interest in similar liaison between the substrates of acupuncture and drug addiction that may involve OT. Here, we described the possibility that acupuncture modulates the reinforcing and sensitizing properties of abused drugs in the dopaminergic system via the regulation of activities in the oxytocinergic system. The elements in this paper are summarized as follows : neuroanatomical studies of oxytocinergic innervation and distribution of oxytocin receptors; experiments related to the methamphetamine, cocaine, morphine and ethanol; experiments related to the oxytocin and acupuncture.

• Biomolecules & Therapeutics
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• v.2 no.4
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• pp.316-321
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• 1994

This study was undertaken to estimate whether nalbuphine, a mixed agonist/antagonist opioid analgesic produced psychic dependence. Moreover, the physical dependence liability of nalbuphine was compared with that of morphine after 7 days administrations of the drugs in mice and rats, and the effects of ginseng total saponin (GTS) on the development of physical dependence on nalbuphine were also studied. Nalbuphine did not produce psychic dependence. However, various abstinence signs precipitated by naloxone were observed in nalbuphine-dependent mice and rats. As the nature of the dependence syndrome produced by nalbuphine 30 mg/kg under these conditions seems similar to that induced by morphine 10 mg/kg, it is clear that nalbuphine possesses the substantial abuse potential. Therefore, nalbuphine may be needed to initiate more stringent controls for the prevention of nalbuphine abuse. On the other hand, GTS inhibited the development of physical dependence on nalbuphine and reduced the contents of dopamine and its metabolite in the brains of mice. Accordingly, results of this study suggest that the inhibitory effects of GTS on the development of physical dependence on nalbuphine may involve dopaminergic mechanism. GTS may be useful for the therapy of physical dependence on nalbuphine.

• Biomolecules & Therapeutics
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• v.9 no.2
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• pp.88-95
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• 2001

(+)-Methamphetamine (METH) is a psychostimulant, which has been the most popular abused drug in Korea. The rewarding mechanism in METH abuse has been reported to be mediated by dopaminergic system. Recently, it has been reported that dopamine releaser (phentermine) plays a dominant role in the discriminative stimulus effects of METH, whereas 5-HT releaser (fenfluramine) can strongly modify METH self-administration. The present study is designed to assess the behavioral changes and the changes of the serotonin receptors in the brains of rats administered repeated of self-administered METH. The repeated administration of 1.0 mg/kg/day METH for 12 days increased locomotor activities, and there was no difference between i.v. and i.p. treatment. Rats had actively acquired METH self-administration for 3 weeks at 0.1 or 0.2 mg/kg/injection. Whereas, it was taken few days to acquire sucrose pellet self-administration. The binding of [$^3$H]-8-hydroxy-DPAT (5-H $T_{1A}$ receptors) and [$^3$H]-5-carboxytryptamine (5-H $T_{1B}$ receptors) to brain sections was examined. Both passive administration and self-administration of METH did not change significantly the serotonin receptors levels in hippocampus, striatum and nucleus accumbens. These results suggest that serotonin receptors may not change in the acquisition period of METH self-administration, and we are trying to investigate the serotonin receptors levels of brain in rats maintained of METH self-administration.n.n.

• The Journal of Korean Physical Therapy
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• v.32 no.6
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• pp.388-390
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• 2020

Objectives: The nigrostriatal tract (NST) connect from the substantia nigra pars compacta to the striatum. A few previous studies have reported on the NST in the Parkinson's disease using a proboblistic tractography method. However, no study has been conducted for identification of the NST using streamline DTT technique. In the current study, we used streamline DTI technique to investigate the reconstruction method and characteristics of the NST in normal subjects. Methods: Eleven healthy subjects were recruited in this study. The NST from the substantia nigra of the midbrain and the striatum of basal ganglia was reconstructed using DTI data. Fractional anisotropy, apparent diffusion coefficient (ADC) values and fiber numbers of the NST were measured. Results: In all subjects, the NST between the substantia nigra of the midbrain and the striatum. Mean values for FA, ADC, and tract volume were 0.460, 0.818, and 154.3 in the right NST, and 0.485, 0.818, and 176.3 in the left NST respectively. Conclusions: we reconstructed the NRT from the substantia nigra of the midbrain and the striatum of the basal ganglia using streamline tractography method. We believe that the findings and the proposed streamline reconstruction method of this study would be useful in future researches on the NST of the human brain.

• BMB Reports
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• v.52 no.4
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• pp.250-258
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• 2019

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by selective and progressive loss of dopaminergic neurons. Genetic and environmental risk factors are associated with this disease. The genetic factors are composed of approximately 20 genes, such as SNCA, parkin, PTEN-induced kinase1 (pink1), leucine-rich repeat kinase 2 (LRRK2), ATP13A2, MAPT, VPS35, and DJ-1, whereas the environmental factors consist of oxidative stress-induced toxins such as 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), rotenone, and paraquat. The analyses of their functions and mechanisms have provided important insights into the disease process, which has demonstrated that these factors cause oxidative damage and mitochondrial dysfunction. The most invaluable studies have been performed using disease model organisms, such as mice, fruit flies, and worms. Among them, Drosophila melanogaster has emerged as an excellent model organism to study both environmental and genetic factors and provide insights to the pathways relevant for PD pathogenesis, facilitating development of therapeutic strategies. In this review, we have focused on the fly model organism to summarize recent progress, including pathogenesis, neuroprotective compounds, and newer approaches.

• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.90-97
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• 2022

Recently, increasing evidence suggests that neuroinflammation may be a critical factor in the development of Parkinson's disease (PD) in addition to the ratio of acetylcholine/dopamine because dopaminergic neurons are particularly vulnerable to inflammatory attack. In this study, we investigated whether botulinum neurotoxin A (BoNT-A) was effective for the treatment of PD through its anti-neuroinflammatory effects and the modulation of acetylcholine and dopamine release. We found that BoNT-A ameliorated MPTP and 6-OHDA-induced PD progression, reduced acetylcholine release, levels of IL-1β, IL-6 and TNF-α as well as GFAP expression, but enhanced dopamine release and tyrosine hydroxylase expression. These results indicated that BoNT-A had beneficial effects on MPTP or 6-OHDA-induced PD-like behavior impairments via its anti-neuroinflammation properties, recovering dopamine, and reducing acetylcholine release.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.334-339
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• 2022

Peroxiredoxin 6 (PRDX6) is a bifunctional protein with both glutathione peroxidase and calcium-independent phospholipase activity. Recently, we reported that PRDX6 plays an important role in dopaminergic neurodegeneration in Parkinson's disease. However, the relationship between PRDX6 function and emotional behavior remains elusive. In the present study, we examined depression- and anxiety-like behaviors in PRDX6-overexpressing transgenic (PRDX6-Tg) mice using the forced swim test, tail suspension test, open field paradigm, and elevated plus-maze. PRDX6-Tg mice exhibited depression-like behaviors and low anxiety. In particular, female PRDX6-Tg mice exhibited anxiolytic behavior in the open field test. Furthermore, the serotonin content in the cortex and 5-hydroxytryptophan-induced head twitch response were both reduced in PRDX6-Tg mice. Interestingly, levels of dopa decarboxylase expression in the cortex were decreased in male PRDX6-Tg mice but not in female mice. Our findings provide novel insights into the role of PRDX6 in 5-HT synthesis and suggest that PRDX6 overexpression can induce depression-like behaviors via downregulation of the serotonergic neuronal system.

• Biomolecules & Therapeutics
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• v.30 no.5
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• pp.409-417
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• 2022

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, and accumulating evidence indicates that mitochondrial dysfunction is associated with progressive deterioration in PD patients. Previous studies have shown that sinapic acid has a neuroprotective effect, but its mechanisms of action remain unclear. The neuroprotective effect of sinapic acid was assayed in a PD mouse model generated by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as well as in SH-SY5Y cells. Target protein expression was detected by western blotting. Sinapic acid treatment attenuated the behavioral defects and loss of dopaminergic neurons in the PD models. Sinapic acid also improved mitochondrial function in the PD models. MPTP treatment increased the abundance of mitochondrial fission proteins such as dynamin-related protein 1 (Drp1) and phospho-Drp1 Ser616. In addition, MPTP decreased the expression of the REV-ERB α protein. These changes were attenuated by sinapic acid treatment. We used the pharmacological REV-ERB α inhibitor SR8278 to confirmation of protective effect of sinapic acid. Treatment of SR8278 with sinapic acid reversed the protein expression of phospho-Drp1 Ser616 and REV-ERB α on MPTP-treated mice. Our findings demonstrated that sinapic acid protects against MPTP-induced PD and these effects might be related to the inhibiting abnormal mitochondrial fission through REV-ERB α.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.102-102
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• 1995

The present study was undertaken to investigate the behavioral and biochemical effects of ginseng total sponin (GTS) on methamphetamine-treated mice. GTS (50 or 100 mg/kg) was administered intraperitoneally two times with 2 hour interval. Two hours after the second injection of GTS, methamphetamine (2 mg/kg) was administered subcutaneously. The ambulatory activity of mice was measured by the ti1ting-type ambulometer every 10 min. for 1 hour. Methamphetamine-induced hyperactivity was reduced by GTS. in a dose-dependent manner. To study the neurochemical mechanism underlying the GTS effects, monoamine contents were measured from brain tissues. After 45 min. of methamphetamine injection. mice were sacrificed and monoamine contents were determined from the striatum. Biochemical analysis revealed that GTS reduced the methamphetamine- induced increase in striatal dopamine contents. These observations indicate that inhibition of methamphetamine-induced hyperactivity by GTS is mediated by the modulation of dopaminergic nervous system, and it could be helpful for the therapy of hyperactivity.