• KSBB Journal
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• v.20 no.5 s.94
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• pp.363-370
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• 2005

Neural stem cells (NSCs) of the central nervous system (CNS) have raised a great interest not only for their importance in basic neural development but also for their therapeutic potentials in neurologically degenerative diseases such as Parkinson's, Alzheimer and stroke. During the CNS development, two molecular cascades determine specification of midbrain dopamine system. In one pathway, FGF-8, sonic hedgehog and transcription factor Nurr1 specify dopamine neurotransmitter phenotype. In the other, transcription factors $Lm{\times}lb\;and\;Pt{\times}3$ are required for induction of dopaminergic neurons. In Nurr1 knockout mouse, tyrosine hydroxylase (TH) positive cells fail to appear in substantia nigra, indicating that Nurr1 is essential in specification of dopaminergic cell phenotype. In this study, we used the immortalized human NSCs retrovirally transduced with Nurr1 gene to probe the Nurr1 mediated mechanism to induce dopamine phenotype. While Nurr1 over-expression alone did not generate dopamine phenotype in NSCs, applications of retinoid and forskolin induced expression of TH and AADC mRNAs. In addition, co-cultures of Nurr1 expressing NSCs with human astrocytes induced a marked increase of TH expression. In this co-culture system, the addition of retinoid and forskolin dramatically increased expression of TH. These results indicate that the immortalized human NSCs with Nurr1 gene could have a clinical utility for cell replacement for the Parkinson patients.

• Journal of Korean Medicine Rehabilitation
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• v.19 no.2
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• pp.73-88
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• 2009

Objectives : Neuronal changes that result from treadmill exercise for patients with Parkinson's disease(PD) have not been well documented, although some clinical and laboratory reports suggest that regular exercise may produce a neuroprotective effect and restore dopaminergic and motor functions. However, it is not clear if the improvements are due to neuronal alterations within the affected nigrostriatal region or result from a more general effect of exercise on affect areas and motivation. In this study, we demonstrate that motorized treadmill exercise improves the neuronal outcomes in rodent models of PD. Methods : We used a chronic mouse model of parkinsonism, which was induced by injecting male C57BL/6 mice with 10 doses(Every 12 hour) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (30 mg/kg) and probenecid (20 mg/kg) over 5 days. These mice were able to sustain an exercise training program on a motorized rodent treadmill at a speed of 18 m/min, $0^{\circ}$ of inclination, 40 min/day, 5 days/week for 4 weeks. At the end of exercise training, we extracted the brain and compared their neuronal and neurochemical changes with the control(saline and sedentary) mice groups. Synphilin protein is the substance that manifestly reacts with ${\alpha}$-synuclein. In this study, we used Synphilin as a manifest sign of recovery from neurodegeneration. We analyze the brain stems of the substantia nigra and striatum region using the western blotting technique. Results : There were no expression of synphilin in the saline-induced groups. The addition of MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) greatly accelerated synphilin expression which meant an aggregation of ${\alpha}$-synuclein. But, the MPTP-induced treadmill exercise group showed significantly lower expression than the MPTP-induced sedentary group. This means treadmill exercise has a definite effect on the decrease of ${\alpha}$-synuclein aggregation. Conclusions : In this study, our results suggest that treadmill exercise promoted the removal of the aggregation of ${\alpha}$-synuclein, resulting in protection against disease development and blocks the apoptotic process in the chronic parkinsonian mice brain with severe neurodegeneration.

• Investigative Magnetic Resonance Imaging
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• v.2 no.1
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• pp.14-30
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• 1998

Manganese is an essential element in the body. It is mainly deposited in the liver and to a lesser degree in the basal ganglia of the brain and eliminated through the bile duct. Rapid turnover of managanese in the body makes it difficult to evaluate the manganese exposure in workers, esecially in those with irregular or intermittent exposure, like welders. Therefore, conventional biomarkers, including blood and urine manganese can provide only a limited information about the long-tern or cumulative exposure to manganese. Introduction of magnetic resonance imaging (MRI) made a progress in the assessment of manganese exposure in the medical conditions related to manganese accumulation, e. g. hepatic failure and long-term total parenteral nutrition. Manganese shortens spin-lattice(T1) relaxation time on MRI due to its paramagnetic property, resulting in high signal intensity (HSI) on T1-weighted image(T1W1) of MRI. Manganese deposition in the brain, therefore, can be visualizedas an HSI in the globus pallidus, the substantia nigra, the putamen and the pituitary. clinical and epidemiologic studies regarding the MRI findings in the cases of occupational and non-occupational manganese exposure were reviewed. relationships between HSI on T1W1 of MRI and age, gender, occupational manganese exposure, and neurological dysfunction were analysed. Relationships betwen biological exposure indices and HSI on MRE werealso reviewed. Literatures were reviewed to establish the relationships between HSI, Manganese deposition in the brain, pathologic findings, and neurological dysfunction. HSI on T1W1 of MRI reflects regional manganese deposition in the brain. This relationship enables an estimation of regional manganese deposition in the brain by analysing MR signal intensity. Manganese deposition in the brain can induce a neuronal loss in the basal ganglia but functional abnormality is supposed to be related to the cumulative exposure of manganese in the brain, use of brain MRI for the assessment of exposure in a group of workers seems to be hardly rationalized, while ti can be a useful adjunct for the evaluation of manganese exposure int he cases with suspected manganese-related health problems.