• BMB Reports
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• v.54 no.12
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• pp.592-600
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• 2021

Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the elderly population and is caused by the loss of dopaminergic neurons. PD has been predominantly attributed to mitochondrial dysfunction. The structural alteration of α-synuclein triggers toxic oligomer formation in the neurons, which greatly contributes to PD. In this article, we discuss the role of several familial PD-related proteins, such as α-synuclein, DJ-1, LRRK2, PINK1, and parkin in mitophagy, which entails a selective degradation of mitochondria via autophagy. Defective changes in mitochondrial dynamics and their biochemical and functional interaction induce the formation of toxic α-synuclein-containing protein aggregates in PD. In addition, these gene products play an essential role in ubiquitin proteasome system (UPS)-mediated proteolysis as well as mitophagy. Interestingly, a few deubiquitinating enzymes (DUBs) additionally modulate these two pathways negatively or positively. Based on these findings, we summarize the close relationship between several DUBs and the precise modulation of mitophagy. For example, the USP8, USP10, and USP15, among many DUBs are reported to specifically regulate the K48- or K63-linked de-ubiquitination reactions of several target proteins associated with the mitophagic process, in turn upregulating the mitophagy and protecting neuronal cells from α-synuclein-derived toxicity. In contrast, USP30 inhibits mitophagy by opposing parkin-mediated ubiquitination of target proteins. Furthermore, the association between these changes and PD pathogenesis will be discussed. Taken together, although the functional roles of several PD-related genes have yet to be fully understood, they are substantially associated with mitochondrial quality control as well as UPS. Therefore, a better understanding of their relationship provides valuable therapeutic clues for appropriate management strategies.

• Korean Journal of Acupuncture
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• v.39 no.2
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• pp.34-42
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• 2022

Objectives : Parkinson's disease (PD) is a neurodegenerative disease caused by dopaminergic neuronal death in the substantia nigra pars compacta. PD is known to be linked with mitochondrial dysfunction and increased oxidative stress. In this study, anti-cytotoxic and anti-oxidative effect of 12 herbal formulae were compared. Methods : According to experts' advice, 12 types of herbal formulae (Gamisoyosan, Galgeuntang, Galgeunhaegitang, Banhabaekchoolcheonmatang, Bojungikgitang, Boheotang, Sihogyejitang, Sihosogantang, Sihocheonggantang, Ojeoksan, Cheongsanggyeontongtang and Palmultang) were selected from 56 types of herbal formulae covered by the National Health Insurance Service in Korea. To detect anti-oxidative effect, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was performed, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to detect anti-cytotoxic effect of 12 herbal formulae using SH-SY5Y human neuroblastoma cells. Results : In DPPH assay, anti-oxidant activity was increased in a dose-dependent manner and half maximal inhibitory concentration was highest in the order of Galgeuntang, Gamisoyosan, Galgeunhaegitang, Ojeoksan, Palmultang, Sihogyejitang, Sihosogantang, Cheongsanggyeontongtang, Sihocheonggantang, Bojungikgitang, Boheotang and Banhabaekchoolcheonmatang. In MTT assay, concentration of 80% cell survival was highest in the order of Sihosogantang, Cheongsanggyeontongtang, Sihocheonggantang, Sihogyejitang, Bojungikgitang, Galgeuntang, Ojeoksan, Boheotang, Palmultang, Galgeunhaegitang, Banhabaekchoolcheonmatang and Gamisoyosan. Formulae with more than 50% DPPH radical scavenging activity at concentrations for 80% cell survival were Sihosogantang, Cheongsanggyeontongtang, Sihogyejitang, Galgeuntang and Sihocheonggantang. Conclusions : Sihosogantang, Cheongsanggyeontongtang, Sihogyejitang, Galgeuntang and Sihocheonggantang extracts can be candidate medicines for PD, but the effect should be validated in PD models.

• BMB Reports
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• v.56 no.3
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• pp.202-207
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• 2023

We investigated the neuroprotective effects of deca nano-graphene oxide (daNGO) against reactive oxygen species (ROS) and inflammation in the human neuroblastoma cell line SH-SY5Y and in the 6-hydroxydopamine (6-OHDA) induced Parkinsonian rat model. An MTT assay was performed to measure cell viability in vitro in the presence of 6-OHDA and/or daNGO. The intracellular ROS level was quantified using 2',7'-dichlorofluorescein diacetate. daNGO showed neuroprotective effects against 6-OHDA-induced toxicity and also displayed ROS scavenging properties. We then tested the protective effects of daNGO against 6-OHDA induced toxicity in a rat model. Stepping tests showed that the akinesia symptoms were improved in the daNGO group compared to the control group. Moreover, in an apomorphine-induced rotation test, the number of net contralateral rotations was decreased in the daNGO group compared to the control group. By immunofluorescent staining, the animals in the daNGO group had more tyrosine hydroxylase-positive cells than the controls. By anti-Iba1 staining, 6-OHDA induced microglial activation showed a significantly decrease in the daNGO group, indicating that the neuroprotective effects of graphene resulted from anti-inflammation. In conclusion, nano-graphene oxide has neuroprotective effects against the neurotoxin induced by 6-OHDA on dopaminergic neurons.

• Journal of Korea Society of Industrial Information Systems
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• v.28 no.2
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• pp.31-45
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• 2023

This study deals with exploring qualitative steps and paths that appear as YouTube users' usage time increases quantitatively. For the study, I applied theories from psychology and neuroscience, subdivided the interval between the personalization algorithm of the recommendation system, and active use and analyzed the relationship between variables in this process. According to the theory behavioral model theory (FBM), variable reward, and dopamine addiction were applied. Personalization algorithms easy clicks as triggers according to associated content presentation functions in behavioral model theory (FBM). Variable rewards increase motivational effectiveness with unpredictability of the content you search, and dopamine nation is summarized as stimulating the dopaminergic nerve to continuously and actively consume content. This study is expected to make an academic and practical contribution in that it divides the purpose of use of content in the personalization algorithm and active use section into four stages from a psychological perspective: first use, reuse, continuous use, and active use, and analyzes the path.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.552-560
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• 2023

Background: Ginseng Radix (Panax ginseng Meyer, Araliaceae) has been used medicinally to treat the brain and nervous system problems worldwide. Recent studies have revealed physiological effects that could potentially benefit cognitive performance or mood. The present study aimed to investigate the antidepressant effects of Korean red ginseng water extract (KGE) and its active component in an unpredictable chronic mild stress (UCMS)-induced animal model and elucidate the underlying mechanisms. Methods: The antidepressant potential of the UCMS model was evaluated using the sucrose preference test and open field tests. The behavioral findings were further corroborated by the assessment of neurotransmitters and their metabolites from the prefrontal cortex and hippocampus of rats. Three doses of KGE (50, 100, and 200 mg/kg) were orally administered during the experiment. Furthermore, the mechanism underlying the antidepressant-like action of KGE was examined by measuring the levels of brain-derived neurotrophic factor (BDNF)/CREB, nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap1) proteins in the prefrontal cortex of UCMS-exposed rats. Results: KGE treatment normalized UCMS-induced depression-related behaviors. Neurotransmitter studies conducted after completing behavioral experiments demonstrated that KGE caused a reduction in the ratio of serotonin and dopamine, indicating a decrease in serotonin and dopamine turnover. Moreover, the expression of BDNF, Nrf2, Keap1 and AKT were markedly increased by KGE in the prefrontal cortex of depressed rats. Conclusion: Our results provide evidence that KGE and its constituents exert antidepressant effects that mediate the dopaminergic and serotonergic systems and expression of BDNF protein in an animal model.

• Physical Therapy Rehabilitation Science
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• v.12 no.3
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• pp.207-213
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• 2023

Objective: The purpose of this study was to understand the complex anatomical structure and function of the midbrain to better understand the patient's symptoms and plan effective treatment including pharmacological and rehabilitation interventions. Design: A single case study Methods: A 17-year-old girl presented with acute onset of drowsiness, gait disturbance, mutism, and ptosis. Physical examination revealed postural instability, rigidity of all limbs, and limitations in extraocular movement. The brain MRI revealed an isolated acute infarction in the bilateral midbrain. Considering the location of the infarction, the presenting symptoms were the result of an impairment of the dopaminergic pathway in addition to lesions in the nuclei of the oculomotor nerve. Levodopa/carbidopa was prescribed. And the intensive and comprehensive rehabilitation program was done. Results: As a result of the study, through comprehensive intervention, which encompassed assessments such as the manual muscle test, Korean Modified Barthel Index score, and Trail-making test, significant enhancements in the patient's condition were observed. These findings provide evidence supporting the effectiveness of the intervention in promoting the patient's physical functioning and overall well-being. Conclusions: The results of this case highlight the significance of comprehending the intricate anatomical structure and functional aspects of the midbrain, which led us to approach appropriate pharmacological and rehabilitation interventions. Through active communication among the medical team, we were able to establish a therapeutic plan, which demonstrated that effective treatment can be achieved.

• The Korean Journal of Pain
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• v.37 no.1
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• pp.26-33
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• 2024

Background: Sitagliptin is an antidiabetic drug that inhibits dipeptidyl peptidase-4 enzyme. This study aimed to investigate the antinociceptive and anti-inflammatory effects of sitagliptin in formalin and carrageenan tests and determine the possible mechanism(s) of its antinociceptive activity. Methods: Male Swiss mice (25-30 g) and male Wistar rats (180-220 g) were used for formalin and carrageenan tests, respectively. In the formalin test, paw licking time and in the carrageenan test, paw thickness were considered as indexes of pain behavior and inflammation respectively. Three doses of sitagliptin (2.5, 5, and 10 mg/kg) were used in these tests. Also, several antagonists and enzyme inhibitors were used to evaluate the role of adrenergic, serotonergic, dopaminergic, and opioid receptors as well as the NO/cGMP/K_ATP pathway in the antinociceptive effect of sitagliptin (5 mg/kg). Results: Sitagliptin showed significant antinociceptive and anti-inflammatory effects in the formalin and carrageenan tests respectively. In the carrageenan test, all three doses of sitagliptin significantly (P < 0.001) reduced paw thickness. Pretreatment with yohimbine, prazosin, propranolol, naloxone, and cyproheptadine could not reverse the antinociceptive effect of sitagliptin (5 mg/Kg), which indicates that adrenergic, opioid, and serotonin receptors (5HT₂) are not involved in the antinociceptive effects. L-NAME, methylene blue, glibenclamide, ondansetron, and sulpiride were able to reverse this effect. Conclusions: NO/cGMP/K_ATP, 5HT₃ and D₂ pathways play an important role in the antinociceptive effect of sitagliptin. Additionally significant anti-inflammatory effects observed in the carrageenan test might contribute in reduction of pain response in the second phase of the formalin test.

• Journal of The Korean Society of Clinical Toxicology
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• v.21 no.2
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• pp.81-91
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• 2023

Purpose: Edible insect extracts have been used as an alternative source for medicinal supplements due to their significant antioxidative and anti-inflammatory activity. Recent studies have reported that anti-microbial peptides from insects have neuroprotective effects on dopamine toxins. The purpose of this study was to investigate the protective functions of mealworm (Tenebrio molitor) extract (MWE) on N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced cellular toxicity in SH-SY5Y neuroblastoma cells. Methods: Cellular toxicity induced by the MPTP toxin and the impact of MWE on cell survival were analyzed using MTT assays. DAPI staining was performed to observe apoptotic phenomena caused by MPTP. Changes in caspase-3 activity and protein expression were observed using enzyme activity assays and western blot assays, respectively. Results: MWE exerted significant antioxidant activity, which was measured by both DPPH and ABTS radical assays, with a dose-dependent relationship. Furthermore, MWE resulted in cellular proliferation in SHSY5Y cells in a dose-dependent manner. Furthermore, MWE pretreatment significantly inhibited MPTP-induced cytotoxicity, with a dose-dependent relationship. The morphological characteristics of apoptosis and increased reactive oxygen species induced by MPTP were also significantly reduced by MWE pretreatment. Conclusion: MWE treatment significantly attenuated MPTP-induced changes in the levels of proteins associated with apoptosis, such as caspase-3 and PARP. These findings suggest that MWE exerts neuroprotective effects on human neuroblastoma SH-SY5Y cells subject to MPTP-induced dopaminergic neurodegeneration.

• The Korean Journal of Pharmacology
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• v.22 no.2
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• pp.79-87
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• 1986

Recently it has been shown that central dopaminergic system regulates the renal function and that intracerebroventricularly (icv) administered dopamine (DA) produces antidiuresis and antinaturiuresis, resembling icv norepinephrine, and evidence has been accumulated which would suggest the involvement of adrenergic system in the DA effects. It was attempted therefore in this study to see whether the DA effect is influenced by pretreatment of yohimbine which is known as a specific ${\alpha}_2-adrenoceptor$ antagonist. Yohimbine produced, when given icv in doses of $100\;{\mu}g/kg$, marked antidiuresis and antinatriuresis along with decreases in renal perfusion and glomerular filtration. DA, in doses of $15\;{\mu}g/kg$, also produced antidiuresis and antinaturiuresis. However, after yohimbine-pretreatment DA $15\;{\mu}g/kg$ improved renal hemodynamics, and electrolyte excretion and urine flow rate transiently increased. With $150\;{\mu}g/kg$ DA, the antidiuresis was more marked in the control group. But the yohimbine-pretreated animals responded with marked diuresis and natriuresis, sodium excretion increasing more than three-fold, which lasted for 20 minutes. $K^+-excretion$, osmolar clearance as well as free-water reabsorption increased. Renal hemodynamics improved partly. Apomorphine, a DA agonist, when given icv in doses of $150\;{\mu}g/kg$, produced diuresis and naturiuresis, concomitant with increased renal hemodynamics. Yohimbine-pretreatment however did not abolish the apomorphine-induced diuresis and naturiuresis. Antidiuresis and antinatriuresis elicited by norepinephrine, $10\;{\mu}g/kg$, was not affected by yohimbine-pretreatment. These results indicate that the renal effects of icv DA is not so simple as those of norepinephrine, and the diuretic natriuretic cffect which had been masked by the hemodynamic effect becomes manifest only when the decreases in hemodynamics were removed by the pretreatment of yohimbine. It was further suggested that those DA receptors which mediate the natriuretic response to icv DA is not affected by yohimbine, whereas those receptors involved in the decrease in renal hemodvnamics are blocked by yohimbine. And the possibility of involvement of adrcnergic system in the DA action is not substantiated.

• The Korean Journal of Nuclear Medicine
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• v.39 no.6
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• pp.421-429
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• 2005

Purpose: It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with dopaminergic neuron and regulates the activation of the dopaminergic system. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with $[^{11}C]raclopride$. Materials and Methods: Five male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of $24.4{\pm}1.7$ years) were enrolled in this study $[^{11}C]raclopride$, a dopamine D2 receptor radioligand, was administrated with bolus-plus-constant infusion. Dynamic PET was performed during 120 minutes ($3{\times}20s,\;2{\times}60s,\;2{\times}120s,\;1{\times}180s\;and\;22{\times}300s$). following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurement of plasma nicotine level were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as (striatal-cerebellar)/cerebellar activity, was measured under equilibrium condition at baseline and smoking session. Results: The mean decrease in binding potential of $[^{11}C]raclopride$ between the baseline and smoking in caudate head, anterior putamen and ventral striatum was 4.7%, 4.0% and 7.8%, respectively. This indicated the striatal dopamine release by smoking. Of these, the reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (Spearman's rho=0.9, p=0.04). Conclusion: These data demonstrate that in vivo imaging with $[^{11}C]raclopride$ PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount or nicotine administered bt smoking.