• The Korea Journal of Herbology
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• v.28 no.5
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• pp.21-28
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• 2013

Objectives : The aim of this study was to investigate the neuroprotective effects and mechanisms of Cyperi Rhizoma extracts (CRE) using in vitro and in vivo models of Parkinson's disease (PD). Methods : We evaluated the neuroprotective effect of CRE against 1-methyl-4-phenylpyridinium (MPP+) toxicity using tyrosine hydroxylase immunohistochemistry (IHC) in primary rat mesencephalic dopaminergic neurons. In addition, the effect of CRE was evaluated in mice PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). For evaluations, C57bl/6 mice were orally treated with CRE 50 mg/kg for 5 days and were injected intraperitoneally with MPTP (20 mg/kg) at 2 h intervals on the last day. To identify the CRE affects on MPTP-induced neuronal loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and striatum of mice, the behavioral tests and IHC analysis were carried out. Also, we conducted nitric oxide (NO) and tumor necrosis factor-alpha (TNF-${\alpha}$) assay in dopaminergic neurons and IHC using glial markers in SNpc of mice to assess the anti-inflammation effects. Results : In primary mesencephalic culture system, CRE protected dopaminergic cells against $10{\mu}M$ MPP+-induced toxicity at 0.2 and $1.0{\mu}g/mL$. In the behavior tests, CRE treated group showed improved motor deteriorations than those in the MPTP only treated group. CRE significantly protected striatal dopaminergic damage from MPTP-induced neurotoxicity in mice. Moreover, CRE inhibited productions of NO and TNF-${\alpha}$ in dopaminergic culture system and activation of astrocyte and microglia in SNpc of the mice. Conclusion : We concluded that CRE shows anti-parkinsonian effect by protecting dopaminergic neurons against MPP+/MPTP toxicities through anti-inflammatory actions.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.39-48
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• 1994

The present study was aimed at establishing what changes occur in the dopamine levels and pattern of TH-immunoreactive neurons of certain areas of rat brain during food intake suppression produced by intraperitoneally administration of CCK-8. CCK-8 in dose of $10\;{\mu}g/kg$ was injected intraperitoneally to 48 h food-deprived rats. In the fasted group, the contents of dopamine were decreased in the frontal, striatum, hypothalamus and amygdala as compared to those of the fed control group. The administration of CCK-8 showed significant decrease on the dopamine levels of the hypothalamus, in comparison to those of the sated and starved group. During deprived condition, the density and number of TH-immunoreactive neurons in the paraventricular nucleus, arcuate nucleus, median eminence and substantia nigra were lower than those of the fed control group. After administration of CCK-8, the pattern and distribution of TH-positive neouons in the hypothalamic areas and substantia nigra were increased when compared to those of the starved group. It is concluded that the results demonstrate the partial involvement of hypothalamic dopamine-containing neurons in the feeding inhibition of CCK-8. Furthermore, the results indicate that TH-immunoreactive neurons play on important role in the hypothalamus and substantia nigra for eating behavior

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.1
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• pp.31-38
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• 2006

Fluoxetine, widely used for the treatment of depression, is known to be a selective serotonin reuptake inhibitor (SSRI), however, there are also reports that fluoxetine has direct effects on several receptors. Employing whole-cell patch clamp techniques in rat brain slice, we studied the effects of fluoxetine on corticostriatal synaptic transmission by measuring the change in spontaneous excitatory postsynaptic currents (sEPSC). Acute treatment of rat brain slice with fluoxetine ($10{\mu}M$) significantly decreased the amplitude of sEPSC ($8.1{\pm}3.3$%, n=7), but did not alter its frequency ($99.1{\pm}4.7$%, n=7). Serotonin ($10{\mu}M$) also significantly decreased the amplitude ($81.2{\pm}3.9$%, n=4) of sEPSC, but did not affect its frequency ($105.8{\pm}8.0$, n=4). The effect of fluoxetine was found to have the same trend as that of serotonin. We also found that the inhibitory effect of fluoxetine on sEPSC amplitude ($93.0{\pm}1.9$%, n=8) was significantly blocked, but not serotonin ($84.3{\pm}1.6$%, n=4), when the brain slice was incubated with p-chloroamphetamine ($10{\mu}M$), which depletes serotonin from the axon terminals and blocks its reuptake. These results suggest that fluoxetine inhibits corticostriatal synaptic transmission through postsynaptic, and that these effects are exerted through both serotonin dependent and independent mechanism.

• 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.

• Journal of Oriental Neuropsychiatry
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• v.8 no.1
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• pp.49-68
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• 1997

This study aimed to evaluate the anti-stress effect of Yangsimtang and Yangsimtang+Siyup on the rats in immobilization stress.The experimental animals were immobilized in the stress box(5${\times}$5${\times}$20cm) for 12 hours in a day suring 3 days, and administered 1ｇ/100ｇ of Yangsimtang and Yangsimtang+Siyup and Siyup extract for 12 days before stress. The norepinephrine, epinephrine, dopamine and serotonin contents were measured by HPLC method in various part of rat brain.The following results were observed.1. In frontal cortex the norepinephrine content of control group was 561.${\pm}$24.46 ng/g brain tissue, that of saple 1 group was 430.8$\pm$41.2 ng/g brain tissue, and that of sample 2 group was 417.2$\pm$38.5 ng/g brain tissue. The differences was statistically significant.2. In corpus striatum, the norepinephrine content of control group was 561.3$\pm$27.3 ng/g brain tissue, and that of sample 1 group was 422.1$\pm$21.2 ng/g brain tissue, the dopamine content of control group was 1205.1$\pm$75.9 ng/g brain tissue, that of sample 2 group was 685.6$\pm$41.5 ng/g brain tissue. The differences was statistically significant.3. In hypothalamus, the norepinephrine content of control group was 1165.1$\pm$162.6 ng/g brain tissue, that of sample 2 group was 947.2$\pm$35.7 ng/g brain tissue. The differences was statistically significant.4. In hippocampus, the norepinephrine content of control group was 931.6$\pm$82.2 ng/g brain tissue, that of sample 1 group was 652.1$\pm$47.5 ng/g brain tissue, and that of sample 2 group was 627.4$\pm$31.2 ng/g brain tissue, the dopamine contrnt of control group was 315.4$\pm$28.4 ng/g brain tissue, that of sample 2 group was 208.5$\pm$23.7 ng/g brain tissue. The differences were statistically significant.Base on the above results, it may be concluded that Yangsimtang and Yangsimtang+Siyup are effective to reduce stress.

• The Journal of Internal Korean Medicine
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• v.21 no.1
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• pp.116-125
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• 2000

Objectives : The aim of this study is to investigate that Sunghyangjeongki-San which has been frequently medicated in the early stage of stroke can protect against ischemic damage in rat brain Methods : Extracellular levels of amino acids(glutamate, aspartate, GABA, glycine, taurine, tyrosine, alanine), organic acids(pyruvate, lactate), and cerebral infarction volume were measured at the striatum of rats subjected to permanant focal cerebral ischemia induced by 2 hours of middle cerebral artery occiusion(MCAO). Rats were orally administered with Sunghyangjeongki-San at 30mins before MCAO and the microdialysate was collected by intracerebral microdialysis three times before MCAO and six times after MCAO at 20mins interval and analyzed by HPLC. After a microdialysis study, the brain was sliced and stained with cresyl violet buffer for the measurement of cerebral infarcted area and volume by image analyzer system Results : The concentrations of glutamate, aspartate, and tyrosine known as excitatory neurotransmitters were significantly decreased in Sunghyangjeongki-San group compared with control group, The concentrations of GABA, glycine, taurine and alanine known as inhibitory neurotransmitters were significantly increased in Sunghyangjeongki-San group compared with control group. The concentrations of pyruvate and lactate showed little significant change in Sunghyangjeongki-San group compared with control group. The measurement of cerebral infarcted area and volume by image analyzer system were significantly decreased in Sunghyangjeongki-San group compared with control group. Conclusions : Sunghyangjeongki-San can affect on protecting against cerebral ischemia by regulating extracellular levels of excitatory and inhibitory amino acid neurotransmitters and improve the conditions of the patients in the early stage of stroke.

• The Korea Journal of Herbology
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• v.29 no.3
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• pp.27-33
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• 2014

Objectives : The aim of this study was to investigate the protective effect of extract of Thuja orientalis leaves (TOFE) against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity by inhibition of inflammation in in vitro and in vivo models of Parkinson's disease (PD). Methods : We evaluated the effect of TOFE against lipopolysaccharide (LPS)/1-methyl-4-phenylpyridinium ($MPP^+$) toxicity using nitric oxide (NO) assay, inducible NO synthase and cyclooxygenase 2 western blot, tyrosine hydroxylase and microglia activation immunohistochemistry (IHC) in BV2 cell, primary rat mesencephalic neurons, or C57BL/6 mice. We also evaluated the effect of TOFE in mice PD model induced by MPTP. C57BL/6 mice were treated with TOFE 50 mg/kg for 5 days and were injected intraperitoneally with four administrations of MPTP on the last day. We conducted behavioral tests and IHC analysis to see how TOFE affect MPTP-induced neuronal loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and striatum (ST) of mice. To assess the anti-inflammation effects, we carried out glial fibrillary acidic protein and macrophage-1 antigen integrin alpha M in IHC in SNpc and ST of mice. Results : In an in vitro system, TOFE decreasesd NO generations in BV2 cells. TOFE protected dopaminergic cells against LPS or $MPP^+$-induced toxicity in primary mesencephalic dopaminergic neurons. In vivo system, TOFE at 50 mg/kg treated group showed improved motor deteriorations than the MPTP only treated group and TOFE significantly protected striatal dopaminergic damage from MPTP-induced neurotoxicity in mice. Moreover, TOFE inhibited activation of astrocyte and microglia in SNpc and ST of the mice. Conclusions : We concluded that TOFE showed anti-parkinsonian effect by protection of dopaminergic neurons against MPTP toxicity through anti-inflammatory actions.

• The Korean Journal of Nuclear Medicine
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• v.39 no.6
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• pp.445-455
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• 2005

Purpose: We developed an animal SPECT system using clinical Philips ARGUS scintillation camera and pinhole collimator with specially manufactured small apertures. In this study, we evaluated the physical characteristics of this system and biological feasibility for animal experiments. Materials and Methods: Rotating station for small animals using a step motor and operating software were developed. Pinhole inserts with small apertures (diameter of 0.5, 1.0, and 2.0 mm) were manufactured and physical parameters including planar spatial resolution and sensitivity and reconstructed resolution were measured for some apertures. In order to measure the size of the usable field of view according to the distance from the focal point, manufactured multiple line sources separated with the same distance were scanned and numbers of lines within the field of view were counted. Using a Tc-99m line source with 0.5 mm diameter and 12 mm length placed in the exact center of field of view, planar spatial resolution according to the distance was measured. Calibration factor to obtain FWHM values in 'mm' unit was calculated from the planar image of two separated line sources. Te-99m point source with i mm diameter was used for the measurement of system sensitivity. In addition, SPECT data of micro phantom with cold and hot line inserts and rat brain after intravenous injection of [I-123]FP-CIT were acquired and reconstructed using filtered back protection reconstruction algorithm for pinhole collimator. Results: Size of usable field of view was proportional to the distance from the focal point and their relationship could be fitted into a linear equation (y=1.4x+0.5, x: distance). System sensitivity and planar spatial resolution at 3 cm measured using 1.0 mm aperture was 71 cps/MBq and 1.24 mm, respectively. In the SPECT image of rat brain with [I-123]FP-CIT acquired using 1.0 mm aperture, the distribution of dopamine transporter in the striatum was well identified in each hemisphere. Conclusion: We verified that this new animal SPECT system with the Phlilps ARGUS scanner and small apertures had sufficient performance for small animal imaging.

• The Korean Journal of Nuclear Medicine
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• v.31 no.1
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• pp.9-18
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• 1997

The therapeutic efficacy of antipsychotic drugs is generally attributed to their ability to block dopamine $D_2$ receptors. Classical $D_2$ antagonists are not effective to treat negative symptoms and produce extrapyramidal side effects On the other hand, atypical antipsychotic agents ameliorate negative symptoms without producing extra-pyramidal side effects, and it is reported to be associated with blockade of serotonin $5-HT_2$ receptors. The purpose of this study was to evaluate the effect of risperidone on neuroreceptors in the rat brain by Quantitative autoradiography method. In acute treatment group, risperidone was injected into Peritoneal cavity of male Wistar rats with dose of 0, 0.1, 0.25, 0.5, 1.0 and 2.0mg/kg in each group(5/group), and they were decapitated after 2 hours. In chronic treatment group, risperidone was injected with dose of 0, 0.1, and 1mg/kg(I.P.) for 21 days and decapitated after 24 hours following last treatment. The effect of risperodone on the binding of [$^3H$]spiperone to $5-HT_2$ and $D_2$ receptors were analysed in 4 discrete regions of the striatum, nucleus accumbens, and frontal cortex by quantitative autoradiography Acute treatment with risperidone reduced cortical $5-HT_2$ specific [$^3H$]spiperone binding to 32% of vehicle-treated control. Subcortical $5-HT_2$ specific [$^3H$]spiperone binding was not affected at all dose groups whereas a significant reduction (57%) in $D_2$ specific [$^3H$]spiperone binding was observed in risperidone treated group at doses of 1-2mg/kg. Chronic treatment with risperidone produced a decrease in the maximal number of cortical $5-HT_2$ receptors to 51% and 46% of control in 0.1mg/kg & 1mg/kg treated group respectively. In conclusion, risperidone is a cortical serotonin receptor antagonist with relatively weak antagonistic action on dopamine receptors. These effects oil neuroreceptors may explain the therapeutic effect of risperidone as a atypical antipsychotic agents.

• Neonatal Medicine
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• v.15 no.1
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• pp.32-37
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• 2008

Purpose : Perinatal asphyxia is an important cause of neonatal mortality and subsequent lifelong neurodevelopmental handicaps. Although many treatment strategies have been tested, there is currently no clinically effective treatment to prevent or reduce the harmful effects of hypoxia and ischemia in humans. In the clinical setting, maternal hyperthermia induces adverse effects on the neonatal brain, but recent studies have shown that hyperthermic pretreatment (PT) plays some role in hypoxic-ischemic (HI) injuries of the developing brain. The present study investigated the effect of hyperthermic PT on HI brain injuries in newborn rats. Methods : HI was produced in 7-day-old neonatal rats by unilateral common carotid artery ligation, followed by hypoxia with 8% oxygen at $38^{\circ}C$ for 2 hours. Twenty-four hours before HI, one-half of the pups were exposed to a $40^{\circ}C$ environment for 2 hours. The severity of the brain injury was assessed 7 days after the HI. Results : Hyperthermic PT reduced the gross and histopathologic findings of brain injury from 64.7 to 31.2% (P<0.05). There were no differences in location and severity of injury between the pretreated and control brains. Conclusion : These findings indicate that hyperthermic PT provides neuroprotective benefits on HI in the developing brain. Also, these findings suggest maternal hyperthermia may have protective effect on perinatal HI brain injuries.