• The Korean Journal of Physiology and Pharmacology
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• v.8 no.5
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• pp.245-251
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• 2004

The effects of fetal mesencephalic cell grafts on the restoration of nigrostriatal dopaminergic function were studied in the intrastriatal 6-hydroxydopamine-lesioned rats. Four weeks after lesioning, transplantation of ventral mesencephalic cells from embryonic day 14 fetuses showed the number of tyrosine hydroxylase (TH) positive cells and fiber outgrowth in the grafted striatum, and significantly ameliorated symptomatic motor behavior of the animals, as determined by apomorphine-induced rotation. Furthermore, in substantia nigra pars compacta (SNc), the numbers of TH + cells and fibers were markedly restored. Dopamine content of ipsilateral SNc was close to that of contralateral SNc $(91.9{\pm}9.8%)$ in the transplanted animals, while the ratio was approximately 32% in sham-grafted animals. These results indicate that grafted cells restored the activity for the dopaminergic neurons located in SNc, although they were transplanted into striatum. In addition, we showed that the implanted fetal cells expressed high level of glial cell line-derived neurotrophic factor (GDNF), suggesting that the transplanted fetal cells might serve as a dopamine producer and a reservoir of neurotrophic factors. These results may be helpful in consideration of the therapeutic transplantation at early stage of PD.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.4
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• pp.139-144
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• 2007

Recent studies suggest that alterations in glutamate receptor subunit levels in mesocorticolimbic dopamine areas could account for neural adaptations in response to psychostimulant drugs. Although many drugs of abuse induce changes in ionotropic glutamate receptor subunits in mesocorticolimbic dopamine areas, the changes of ionotropic glutamate receptor subunits by repeated nicotine treatment in these areas are not known. To answer this question, we injected male Sprague-Dawley rats twice daily with nicotine (0.4 mg/kg) or saline (1 ml/kg) for 10 days. The immunoreactivity of NR1, GluR1, and GluR2 glutamate receptor subunits was examined $16{\sim}18 h$ after the last injection of saline or nicotine. Repeated nicotine treatment significantly increased NR1 levels in the ventral tegmental area (VTA). In addition, repeated nicotine treatment showed a tendency towards an increase in GluR1 levels in the VTA as well as in striatum. However, there was no significant change in glutamate receptor subunits in other areas including nucleus accumbens (NAc). These results demonstrate that repeated nicotine treatment increases NR1 levels in VTA similarly to other drugs of abuse, suggesting that elevated glutamate receptor subunits in the VTA, but not NAc may be involved in the excitation of mesocorticolimbic dopamine neurons by nicotine.

• 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.

• Korean Journal of Acupuncture
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• v.38 no.3
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• pp.162-174
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• 2021

Objectives : We aimed to identify the antidepressant effect of liver tonification acupuncture treatment (ACU (LT); KI10, LR8, LU8, LR4) and four gate acupuncture treatment (ACU (FG); LI4, LR3) and its brain neural activity in the normal and chronic restraint stress (CRS)-induced mouse model. Methods : Firstly, normal mice were given ACU (LT) or ACU (FG) and the c-Fos expressions in each brain region were analyzed to examine brain neural activity. Secondly, CRS was administered to mice for 4 weeks, then ACU (LT) or ACU (FG) was performed for 2 weeks. The depression-like behavior was evaluated using open field test (OFT) before and after acupuncture treatment. Then, the c-Fos expressions in each brain region were analyzed to examine brain neural activity. Results : In normal mice, ACU (FG) regulated brain neural activities in the hypothalamus, hippocampus, and periaqueductal gray. ACU (LT) changed more brain regions in the prefrontal cortex, insular cortex, striatum, and hippocampus, including those altered by ACU (FG). In CRS-induced model, ACU (LT) alleviated depression-like behavior more than ACU (FG). Also, brain neural activities in the motor cortex area 2 (M2), agranular ventral part and piriform of insular cortex (AIV and Pir), and cornu ammonis (CA) 1 and CA3 of hippocampus were changed by ACU (LT), and those of AIV and CA3 were also changed by ACU (FG). As in normal mice, ACU (LT) resulted in changes in more brain regions, including those altered by ACU (FG) in CRS model. M2, Pir, and CA1 were only changed by ACU (LT) in depression model, suggesting that these brain regions reflect the specific effect of ACU (LT). Conclusions : ACU (LT) relieved depression-like behavior more than ACU (FG), and this acupuncture effect was associated with modulation of brain neural activities in the motor cortex, insular cortex, and hippocampus.

• Molecules and Cells
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• v.41 no.8
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• pp.742-752
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• 2018

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive degeneration of dopaminergic (DAergic) neurons, particularly in the substantia nigra (SN). Although circadian dysfunction has been suggested as one of the pathophysiological risk factors for PD, the exact molecular link between the circadian clock and PD remains largely unclear. We have recently demonstrated that $REV-ERB{\alpha}$, a circadian nuclear receptor, serves as a key molecular link between the circadian and DAergic systems. It competitively cooperates with NURR1, another nuclear receptor required for the optimal development and function of DA neurons, to control DAergic gene transcription. Considering our previous findings, we hypothesize that $REV-ERB{\alpha}$ may have a role in the onset and/or progression of PD. In the present study, we therefore aimed to elucidate whether genetic abrogation of $REV-ERB{\alpha}$ affects PD-related phenotypes in a mouse model of PD produced by a unilateral injection of 6-hydroxydopamine (6-OHDA) into the dorsal striatum. $REV-ERB{\alpha}$ deficiency significantly exacerbated 6-OHDA-induced motor deficits as well as DAergic neuronal loss in the vertebral midbrain including the SN and the ventral tegmental area. The exacerbated DAergic degeneration likely involves neuroinflammation-mediated neurotoxicity. The $REV-erb{\alpha}$ knockout mice showed prolonged microglial activation in the SN along with the over-production of interleukin $1{\beta}$, a pro-inflammatory cytokine, in response to 6-OHDA. In conclusion, the present study demonstrates for the first time that genetic abrogation of $REV-ERB{\alpha}$ can increase vulnerability of DAergic neurons to neurotoxic insults, such as 6-OHDA, thereby implying that its normal function may be beneficial for maintaining DAergic neuron populations during PD progression.

• Applied Microscopy
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• v.18 no.1
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• pp.1-20
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• 1988

There's been arguments on the different morphological status between the nucleus accumbens septi and nucleus fundus striati of ventral striatum. Authors carried out the comparative study on the neuronal cell types of these nuclei, in the chick and the rat. Results are summarized as follows: In the nucleus accumbens septi of the chick, there found 3 main cell types. Type I cells are oval or spindle-shaped. They are the most abundant cell types, comprising more than 80% of neurons. The pale nucleus is usually indented. The cytoplasm is also pale and contains small amount of mitochondria, rough r-ER and Golgi complexes. This cell has a few symmetric synapses on the cell membrane. Type II cells are pale large cells. They are polygonal or irregularly-shaped. They contain pale spherical nucleus, and the pale cytoplasm with relatively large amount of mitochondria, free ribosomes and well-developed Golgi complexes. Some axo-somatic synapes are found on the cell. Type III cells are oval or spherical-shaped. The nucleus is relatively pale and large, In the dense cytoplasm, well developed. r-ER formed typical Nissl's body, and there found many mitochondria, ribosomes and lysosomes. In the chick fundus striati nucleus, there also found 3 main cell types. Type I cells are small and spindle-shaped. This type is the most abundant one and constitutes more the 80% of the neurons. Morphological features other than it's shape, is generally similar with that of Type I cell in the nucleus accumbens. Type II cells are irregularly shaped large cells. Dense cytoplasm contains large amount of cell organelles. Some axo-somatic synapses are found. Type III cells are small dense cells. This oval cell contains the oval nucleus, and the plentiful cytoplasm with well developed r-ER, ribosomes and mitochondria. In the nucleus accumbens septi of the rat, there found 4 main cell types. Type I cells are small, oval or spherical cells, comprising more than 90% of all the neurons. Spherical nucleus shows typical chromatin rim along the nuclear membrane. Dense cytoplasm contains many ribosomes and mitochondria. Type II cells are large oval cells. The eccentric nucleus is deeply invaginated. Pale cytoplasm contains large amount of ribosomes, Golgi complexes, mitochondria, and dense bodies. Type III cells are pale, large, oval cells. They contain moderate amount of ribosomes and mitochondria, and some scattered stacks of r-ER. Type IV cells are small pale cells. Small oval nucleus is indented and shows chromatin rim. Only small amount of ribosomes and mitochondria can be found. In the nucleus fundus striati of the rat, there also found 4 main cell types. Type I cells are spherical or oval cells, comprising more than 90% of the neurons. The chromatin rim of the spherical nucleus is not so prominent as compared to the rim of type I cell in the nucleus accumbens septi. The cytoplasm contains moderate amount of mitochondria, ribosomes and some scattered r-ER. A few axo-somatic synapses were found. Type II cells are small round or polygonal cells. Golgi complexes are especially well-developed in this cell type. The cytoplasm also contains moderate amount of mitochondria, ribosomes, and dense bodies. Type III cells are small cells. The large nucleus shows prominent chromatin rim. The cytoplasm contains many ribosomes and mitochondria. Type IV cells are large, spheircal or oval cells. The nucleus is deeply indented. The plentiful cytoplasm contains large amount of ribosomes, mitochondria, Golgi complexes, neurotubules, but not r-ER. In the present study, it is clear that the nucleus accumbens septi and the nucleus fundus striati are independant cell groups, according to their cytoarchitectonics and the ultrastructural features of their cell types.