• Korean Journal of Veterinary Research
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• v.40 no.1
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• pp.1-16
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• 2000

Nowadays, mongolian gerbil is notably utilized for the research of brain and water deprivation because of a congenital incomplete willis circle structure in the brain, audiogenic seizure in low noise, and special cholesterol metabolism without water absorption for a long time. In this study, we are intend to identify the morphological changes of the catecholaminergic neuron of brain according to the time lapse in the condition of long term water deprivation. 55 mongolian gerbil were divided 10 groups(control, 1, 2, 3, 4, 5, 10, 15, 20, 42th day water deprivation group), of which each group include 5 mongolian gerbils and 5 normal mongolian gerbils in control group were also used for brain atlas as a control. The brains were observed by the immunohistochemical stain using the TH, DBH and PMNT antibody. The results were as followings; 1. The nerve fibers of the TH-immunoreactive neuron were observed only in the and corpus striatum of the telencephalon. 2. Intensity of the immunostain of the nerve fiber in the cerebral cortex and corpus striatum was decreased gradually day by day after water deprivation. 3. The TH-immunoreactive nerve cells were observed in the paraventricular and periventricular nucleus of the 3rd ventricular in the hypothalamus of mongolian gerbil but the number of nerve cells were decreased from the first day of the water deprivation to the 10th day and increased until the 20th day, after than redecreased from the 20th day by the continuous water deprivation. The number of nerve fibers in this area were increased in the first day, but decreased from the 2nd day of water deprivation. The shape and density of the dopamine secreting cells in the brain of mongolian gerbil by the immunoreactive stain were changed in the continuous water deprivation. In this results, we can conclude that dopamine concerned in the water metabolism of mongolian gerbil, and mongolian gerbil could be used as an animal model for the research of water deprivation.

• Sleep Medicine and Psychophysiology
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• v.15 no.1
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• pp.39-43
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• 2008

Objectives: The pathophysiology of restless legs syndrome (RLS) is not obvious, but many promising theories involve dopaminergic deficiency and genetic causes. The RLS is presumed to occur more frequently among schizophrenic patients who take antipsychotics, most of which blocks the dopamine receptors. This study aimed to investigate whether dopamine transporter gene (DAT1) 40 base pair (bp) variable number of tandem repeat (VNTR) polymorphism is associated with the antipsychotic-induced RLS in schizophrenia. Methods: We determined the diagnosis of RLS among the 190 Korean schizophrenic patients by the diagnostic criteria of the International Restless Legs Syndrome Study Group (IRLSSG). Genotyping was performed for the 40bp VNTR in DAT1 gene using polymerase chain reaction. Results: We separated the schizophrenic patients into 44 patients with RLS and 146 patients without RLS. The genotype and allele frequencies did not differ significantly between two groups. Conclusions: These results suggest that DAT1 gene 40bp VNTR is not associated with the antipsychotic-induced RLS in schizophrenia. To confirm these results, larger-scale association study is needed in the future.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.14-40
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• 2002

15-Deoxy- Δ$\^$12,14/-prostaglandin J$_2$ (15-deoxy-PGJ$_2$), a naturally occurring ligand activates the peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$). Activation of PPAR-y has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-PGJ$_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-PGJ$_2$ (0.2 to 1.6 ${\mu}$M) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/$m\ell$). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-PGJ$_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-PGJ$_2$ (0.8 ${\mu}$M) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-PGJ$_2$ on the expression of p38 MAP kinase and activation of AP-1. The promoting ability of 15-deoxy-PGJ$_2$ did not occur through PPAR-${\gamma}$, as synthetic PPAR-${\gamma}$ agonist and antagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), PPAR-${\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and PGE$_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of 15-deoxy-PGJ$_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-PGJ$_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 signal pathway may be important in the promoting activity of 15-deoxy-PGJ$_2$ on the differentiation of PC12 cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.35 no.2
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• pp.71-80
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• 2021

Parkinson's disease is one of the typical neurodegenerative disease and it is caused by the destruction of substantia nigra in brain leading to lack of dopamine secretion, and it presents 4 major motor symptoms such as tremor, bradykinesia, stiffness, postural instability. Furthermore, it causes many non-motor symptoms such as anosmia, REM sleep conduct disorder, orthostatic hypotension, dementia and autonomic ataxia such as lack of adjusting blood pressure, hyperhydrosis, constipation. Dopaminergic therapy is the most commonly used strategy, but long term treatment of levodopa induce various adverse effects. Thus, many people are focusing on new therapies other than established therapies, and there are many tries and approaches with paradigm shift. Our medical team was able to get 4 cases of PD patients who are hospitalized in our hospital, treated by Whole Body Gi-Hyeol Therapy consisting of acupuncture therapy, herbal therapy, and mental therapy, and their conditions improved in perspective of Unified Parkinson's Disease Rating Scale(UPDRS), Heart Rate Variability(HRV), and Quality of life. Among all 4 cases, UPDRS score and quality of life score is gotton better, and among 2 cases SDNN, RMS-SD, TP, LF, HF scores are finely increased. And PDQ-39 score which shows quality of life is also improved. However, in spite of these improvements and positive results, there were no meaningful improvement in a hurt from a fall which is important to the aged, muscular atrophy which causes bone fracture and SMI(Skeletal Muscle Mass Index) which is indicator of osteoporosis. Thus, supplementary treatment about Whole Body Gi-Hyeol Therapy such as more active nutrition intervention, safe and effective kinesitherapy is needed, and from now on continuous case reports and systematic clinical research which has control group must be carried out.

• Journal of Life Science
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• v.29 no.2
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• pp.191-197
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• 2019

Parkinson's disease (PD) is a progressive neurodegenerative disease that mainly affects motor system with clinical features such as bradykinesia, rigidity, tremor and abnormal posture. PD is characterized by the death of dopaminergic neurons in the substantia nigra pars compacta, which is associated with accumulation of oxidative stress and dysregulation of intracellular signaling pathway. Quercetin-3-O-glucuronide (Q3GA), a major metabolite of quercetin, has been reported to have neuroprotective effects. In this study, we examined the neuroprotective effect of Q3GA against 1-methyl-4-phenyl pyridinium ($MPP^+$)-induced neurotoxicity of PD and the underlying molecular mechanisms in SH-SY5Y cells. MTT and LDH assay showed that Q3GA significantly decreased $MPP^+$-induced cell death, which is accompanied by a reduction in poly (ADP-ribose) polymerase (PARP) cleavage. Furthermore, it attenuated $MPP^+$-induced intracellular reactive oxygen species (ROS) with the reduction of Bax/ Bcl-2 ratio. Moreover, Q3GA significantly increased the phosphorylation of Akt and cAMP response element binding protein (CREB), but it has no effects on the phosphorylation of extracellular signal-regulated kinase (ERK). Taken together, these results demonstrate that Q3GA significantly attenuates $MPP^+$-induced neurotoxicity through ROS reduction and Akt/CREB signaling pathway in SH-SY5Y cells. Our findings suggest that Q3GA might be one of the potential candidates for the prevention and/or treatment of PD.

• Journal of Life Science
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• v.32 no.10
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• pp.771-777
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• 2022

Dopaminergic (DA) cell death in Parkinson's disease (PD) has been attributed to multiple, distinct genetic and environmental factors. In rare familial PD loss of parkin function mutations play a key role in nigral DA neuron-specific pathogenesis primarily via endoplasmic reticulum (ER) stress. In more prevalent sporadic PD, environmental exposure to pesticides has a significant epidemiological role. However, it is largely unknown how environmental exposure to xenobiotics is etiologically linked with the known etiology in familial PD. In the present study biochemical evidence for a common pathogenic mechanism between sporadic and familial PD has been identified employing the recently characterized mesencephalic DA cell line, N27-A. Dieldrin, an organochlorine pesticide epidemiologically implicated in sporadic PD, induced the markers of ER stress response such as a chaperone BiP/Grp78, heme oxygenase-1 and especially, parkin. Accordingly, dieldrin activated the ER resident Caspase-12, a mediator of ER stress-specific apoptosis, during cell death of N27-A cells. Of great interest the dieldrin-induced DA neuronal cell death was synergistically rescued by the overexpression of ER resident neuroprotective proteins, parkin and Bcl-2. The present findings implicate that accumulation of ER stress could be one of common pathogenic mechanisms in idiopathic and familial PD, and some ER proteins, such as parkin and Bcl-2 may effectively attenuate ER stress-mediated N27-A DA cell death.

• Journal of the Korean Society of Radiology
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• v.83 no.3
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• pp.508-526
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• 2022

Parkinson's disease (PD) is a movement disorder that develops due to degenerative loss of dopaminergic cells in the substantia nigra of the midbrain. Recent advances in MRI techniques have demonstrated various imaging findings that can reflect the underlying pathophysiological processes occurring in Parkinson's disease. Many imaging studies have shown that such findings can assist in the diagnosis of Parkinson's disease and its differentiation from atypical parkinsonism. In this review, we present MRI techniques that can be used in clinical assessment, such as nigrosome imaging and neuromelanin imaging, and we provide the detailed imaging features of Parkinson's disease reflecting nigrostriatal degeneration.

• Sleep Medicine and Psychophysiology
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• v.20 no.1
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• pp.15-21
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• 2013

Objectives: Cognitive impairment in restless legs syndrome (RLS) patients can be affected by sleep deprivation, anxiety and depression, which are common in RLS. The objective of this study is to investigate relationship between cognitive impairment and RLS in the non-medicated Korean elderly with controlling for psychiatric conditions. Method: The study sample for this study comprised 25 non-medicated Korean elderly RLS patients and 50 age-, sex-, and education- matched controls. All subjects were evaluated with comprehensive cognitive function assessment tools- including the Korean version of Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K), severe cognitive impairment rating scale (SCIRS), frontal assessment battery (FAB), and clock drawing test (CLOX). Sleep quality and depression were also assessed with Pittsburgh sleep quality index (PSQI) and geriatric depression scale (GDS). Results: PSQI and GDS score showed no difference between RLS and control group. There was no significant difference between two groups in nearly all the cognitive function except in constructional recognition test, in which subjects with RLS showed lower performance than control group (t=-2.384, p=0.02). Subjects with depression ($GDS{\geq}10$) showed significant cognitive impairment compared to control in verbal fluency, Korean version of Mini Mental Status Examination in the CERAD-K (MMSE-KC), word list memory, trail making test, and frontal assessment battery (FAB). In contrast, no difference was observed between subjects who have low sleep quality (PSQI>5) and control group. Conclusions: At the exclusion of the impact of insomnia and depression, cognitive function was found to be relatively preserved in RLS patients compared to control. Impairment of visual recognition in RLS patients can be explained in terms of dopaminergic dysfunction in RLS.

• Applied Microscopy
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• v.30 no.2
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• pp.193-204
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• 2000

Nowadays, mongolian gerbil is widely utilized in the research of brain and water deprivation because of congenitally incomplete Willis' circle, audiogenic seizure in low noise, and special cholesterol metabolism without water absorption for a long time. In this study, we intended to identify the time lapse changes in the general morphoogy and ultrastructure of the catecholaminergic neurons of mongolian gerbil brain in after long-term water deprivation. Fifteen mongolian gerbils were divided into 3 groups (5, 10, and 20-day water deprivation groups), each with 5 mongolian gerbils. Additional 5 mongolian gerbils which received water without limitation were used as a control. The brain sections were immunostained using tyrosine hysroxylase (TH), $ dopamine-\beta-hydroxylase$ (DBH), and phenylethanolamine-N-methyltrasferase (PMNT) antibodies. And immunoreactive cells were observed by electromicroscopy for the ultrastructural changes . The TH-immunoreactive (TH-IR) nerve cells were observed in the para- and peri-ventricular nucleus of the 3 rd ventricle in the hypothalamus and the substantia nigra. The number of TH-IR neurons in these areas was decreased from the 5th day of the water deprivation to the 10 th day and reincreased until 20 th day water deprivation. The shape and density of the dopamine-secreting cells identified by immunohistochemistry showed changes in the continuous water deprivation. Electron microscopy revealed a round nucleus in the neurons of control group but 5-day water deprivation group showed a dense and irregularly shaped nucleus. Also in the 5-day water-deprived group, mitochondria was decreased in number and junctins were disappered. Endoplasmic reticulum, Golgi complex did not show changes after water-deprivation. In this results, we can conclude that dopamine are involved in the water metabolism in mongolian gerbil, and mongolian gerbil could be used as an animal model for the researches of water deprivation.

• Korean Journal of Biological Psychiatry
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• v.13 no.3
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• pp.178-190
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• 2006

Objectives : We investigated the relationship of the alcohol withdrawal symptoms with genetic polymorphism among alcohol dependence patients. Method : The measuring instruments used in this study were the Clinical Institute Withdrawal Assessment for Alcohol(CIWA-Ar). We analyzed DRD2 TaqI A polymorphism, dopamine transporter(DAT 1) polymorphism, and catechol-O-methyltransferase(COMT) polymorphism in 108 male alcoholics and 76 healthy controls. Results : The major findings was as follows. No significant differences for genotype distribution or allele frequency were revealed comparing controls and alcoholic patients. DRD2 Taq I : The subscale score of auditory hallucination among CIWA-Ar scale in homozygote was significantly higher than in heterozygote(OR=1.34). The total score of CIWA-Ar scale in heterozygote was significantly higher than in homozygote. DAT1 : In the subject without DAT-9 gene allele, it was significantly higher of the subscale score of sweating, anxiety among CIWA-Ar scale than in the subject with DAT-9 gene allele. And The total score of CIWA-Ar scale in the subject without DAT-9 gene allele was significantly higher than in the subject with DAT-9 gene allele. COMT : The total score of CIWA-Ar scale in heterozygote was significantly higher than in homozygote. Conclusion : Our results suggest the relationship between specific genetic factors and the withdrawal symptoms of alcohol dependent patients. As the candidate gene of the severity of alcohol withdrawal syndrome, DRD2 Taq1 gene was recommended.