• Biomolecules & Therapeutics
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• v.11 no.4
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• pp.214-223
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• 2003

Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) have become popular recreational drugs of abuse in many countries. Although the neurotoxic damage caused by METH and MDMA is characterized by degeneration of the dopaminergic and serotonergic systems in brain, the molecular and cellular mechanisms remain to be clarified. Therefore, the purposes of this study were to confirm the capability of METH and MDMA to induce apoptosis and to clarify the action of its molecular mechanism by using serotonergic JAR cells and dopaminergic SK-N-SH cells. METH and MDMA were dose-dependently cytotoxic to human serotonergic JAR cells and dopaminergic SK-N-SH cells. The morphological change of apoptosis was found in Giemsa staining and TUNEL and further verified in DNA fragmentation analysis. Immunoblotting analysis revealed proteolytic cleavage of caspase-3 and -9 and change of bcl-2 and bax proteins. These results suggest that METH and MDMA may induce caspase-dependent apoptosis via the mitochondrial cell death pathway and METH and MDMA-induced neurotoxicity may happen to broadly and independently of both dopaminergic and serotonergic systems.

• Molecules and Cells
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• v.42 no.1
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• pp.36-44
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• 2019

Alzheimer's disease (AD) is the most frequent age-related human neurological disorder. The characteristics of AD include senile plaques, neurofibrillary tangles, and loss of synapses and neurons in the brain. ${\beta}-Amyloid$ ($A{\beta}$) peptide is the predominant proteinaceous component of senile plaques. The amyloid hypothesis states that $A{\beta}$ initiates the cascade of events that result in AD. Amyloid precursor protein (APP) processing plays an important role in $A{\beta}$ production, which initiates synaptic and neuronal damage. ${\delta}-Catenin$ is known to be bound to presenilin-1 (PS-1), which is the main component of the ${\gamma}-secretase$ complex that regulates APP cleavage. Because PS-1 interacts with both APP and ${\delta}-catenin$, it is worth studying their interactive mechanism and/or effects on each other. Our immunoprecipitation data showed that there was no physical association between ${\delta}-catenin$ and APP. However, we observed that ${\delta}-catenin$ could reduce the binding between PS-1 and APP, thus decreasing the PS-1 mediated APP processing activity. Furthermore, ${\delta}-catenin$ reduced PS-1-mediated stabilization of APP. The results suggest that ${\delta}-catenin$ can influence the APP processing and its level by interacting with PS-1, which may eventually play a protective role in the degeneration of an Alzheimer's disease patient.

• Journal of Oriental Neuropsychiatry
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• v.32 no.2
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• pp.111-127
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• 2021

Objectives: To review and analyze clinical and preclinical evidence of effectiveness, safety, and underlying mechanisms of yokukansan (YKS), a herbal medicine, in alleviating aggression. Methods: Classical records on YKS were searched in the Korean Traditional Medicine Knowledge Database (KTMKD). By searching five electronic databases, prospective clinical studies and preclinical studies of YKS for alleviating aggression/agitation published up to March 30, 2021 were included. Results: Only two classical records on YKS were found from the KTMKD. A total of 11 clinical studies and 15 preclinical studies were found from the five electronic databases. Among 11 clinical studies, seven enrolled patients with dementia and four enrolled patients with other neuropsychiatric disorders. Most clinical studies reported significant improvement in one or more outcomes related to aggression in the YKS group after treatment. Among 15 preclinical studies, all studies except two reported a significant decrease in aggression/agitation-related behavior of YKS or yokukansankachimpihange. Suggested underlying mechanisms of YKS or yokukansankachimpihange for aggression/agitation in these studies included regulation of serotonin receptor, amelioration of abnormal glucocorticoid level related to the hypothalamic-pituitary-adrenal axis, regulation of orexin secretion, amelioration of degeneration in brain cells including glia cells, and suppression of excessive glutamatergic or dopaminergic activity. Conclusions: There were some clinical and preclinical evidence supporting the effectiveness and safety of YKS for alleviating aggression. Given that aggression is the most frequent and destructive symptoms of behavioral and psychological symptoms of dementia, applicability of YKS as a herbal medicine should be further investigated in future high-quality research.

• Anatomy and Cell Biology
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• v.57 no.3
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• pp.419-430
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• 2024

Huntington's disease (HD) is a hereditary condition considered by the progressive degeneration of nerve cells in the brain, resultant in motor dysfunction and cognitive impairment. Despite current treatment modalities including pharmaceuticals and various therapies, a definitive cure remains elusive. Therefore, this study investigates the therapeutic potential effect of Apelin-13 in HD management. Thirty male Wistar rats were allocated into three groups: a control group, a group with HD, and a group with both HD and administered Apelin-13. Apelin-13 was administered continuously over a 28-day period at a dosage of around 30 mg/kg to mitigate inflammation in rats subjected to 3-NP injection within an experimental HD model. Behavioral tests, such as rotarod, electromyography (EMG), elevated plus maze, and open field assessments, demonstrated that Apelin-13 improved motor function and coordination in rats injected with 3-NP. Apelin-13 treatment significantly increased neuronal density and decreased glial cell counts compared to the control group. Immunohistochemistry analysis revealed reduced gliosis and expression of inflammatory factors in the treatment group. Moreover, Apelin-13 administration led to elevated levels of glutathione and reduced reactive oxygen species (ROS) level in the treated group. Apelin-13 demonstrates neuroprotective effects, leading to improved movement and reduced inflammatory and fibrotic factors in the HD model.

• Applied Microscopy
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• v.36 no.2
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• pp.101-108
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• 2006

Myelin-associated glycoprotein (MAG) has been known to have a crucial role to the formation of myelin sheath during initial stage of myelination. In the present study, we investigated the aging-related expressional changes of MAG in the rat cerebrum. MAG expression was markedly decreased in cerebral cortex by aging. In the adult rat cerebrum, MAG-positive rolls were process-bearing cells with large nucleus, and extensively distributed. However, in the aged rat brain, MAG-positive cells showed small and round morphology with little cytoplasm and few processes. MAG was co-expressed with galatocerebroside, but not with Iba-1, or GFAP. These results suggest that the expressional change of MAG-positive cells is associated with degeneration of oligodendrocyte-myelin system by aging, and that MAG is likely to be a reliable marker for the mature oligodendrocytes in the aged rat brain.

• The Journal of Korean Physical Therapy
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• v.17 no.4
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• pp.589-600
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• 2005

The purposes of this study is to discuss and analyze the effect on the recovery from cut in sciatic nerve. This study used 9 weeks male rats of Sprague-Dawley family. Rat in groups 4 were treated with pulsed therapeutic ultrasound for 3 minutes. 3 times weekly at 3MHz respectively (intensity; $0.2W/cm^2,\;0.5W/Cm^2,\;10W/cm^2$); rat in group 1 received placebo ultrasound. In addition, changes of serum aspartate amino-transferase(AST) and creatine phosphokinase(CPK) levels were also demonstrated with diameter of individual muscle fasciculate and number of muscle fiber in each of three types of muscles located in gastrocnemius, soles. The results of comparing the changes in groups are as follows; 1. We found out that hypertrophic epineurium was present in sciatic nerve injured ultrasound treatment of groups. 2. In the gastrocnemius morphological investigation of the group I (control group), severe muscle atrophy were observed at the 7th days of the sciatic nerve injury. however, muscle atrophy of the group IV ($1.0W/cm^2$) were slightly recovered at the 14th days after treatment ultrasound. At the 28th days, muscular fibers were formed in polygon and were significantly recovered. 3. C-fos immunoreactive of the group II ($0.2W/cm^2$), III ($0.5W/cm^2$) were remarkably increased at the 1th day after treatment of ultrasound. Group IV were markedly deceased. 4. Brain-Derived Neurotrophic Factor(BDNF) immunoreactive of the group II, III were increased after 7 days of the sciatic nerve injury. Group IV were markedly increased from 14th days to 28th days after treatment of ultrasound. 5. A significant increase of serum AST levels were demonstrated in control group. However, serum AST levels of massage groups were significantly decreased compared to that of control group in followed order ; ($0.2W/cm^2<0.5W/cm^2<1.0W/cm^2$). 6. A significant increase of serum CK levels were demonstrated in control of group. However, serum CK levels of massage groups were significantly decreased compared to that of control group in followed order ; ($0.2W/cm^2<0.5W/cm^2<1.0W/cm^2$). The above results suggest that ultrasound treatment after peripheral nerve injury might reduce noxious stimuli, facilitate nerve recovery and effective in the functional improvement delaying muscle atrophy or degeneration.

• Journal of Veterinary Clinics
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• v.14 no.1
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• pp.78-87
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• 1997

The study of present study was to determine the valuable laboratory tests for the differential diagnosis of lead poisoning in dogs. Sixteen mongrel dogs were divided into 2 experimental groups (A and B) and a control group (C). The A and B groups were administered orally 2 mg and 20 mg of lead per kilogram of body weight for 49 days, respectively. In addition to clinical observation, blood, urine and hair samples were collected on appointed day and examined for hematological changes, lead content of serum, whole blood and hair, and urinary $\delta$-aminolevulinic acid concentrations. All dogs were necropside on 49th day and examined for the lead content and histological changes of organs. The results obtained were summarized as follows: The group B showed digestive and nervous signs, and weight loss. The group A showed no significant hematological changes except polychromatophilla on the 7th day. But group B showed polychromatophilia as well as mild anemia and nucleated erythrocyte on the 7th and 35th day. Basophlic stippling erythrocytes were observed in some of the group B on the 14th day. The lead content of whole blood was increased significantly in both A and B groups on the 21the day. The urinary $\delta$-aminolevulinic acid content was increased in both A and B groups on the 7th day. The hair lead content of A and B groups was increased significantly on the 49th and 21th day, respectively. The lead contents of organs including liver, kidney, spleen, muscle and bone were increased significantly in group B. Histopathologic changes were characterized by hemorrhages, necrosis and intranuclear inclusion body in the epithelial cells of convoluted tubles of kidney, cloudy swelling and degeneration and/or necrosis of liver, enlargement of Virchow-Robin space, and swelling of endothelial cells and hyperplasia of the pericytes of brain. From these results it may be concluded that examination of nucleated erythrocyte/polychromatophilia, urinary $\delta$ -aminolevulinic acid, and whole blood and hair lead contents is a reliable clinico-pathological diagnostic methods, and that examination of the Virchow-Robin space, endothelial cells and pericytes of brain as well as intranuclear inclusion body in the epithelial cells of convoluted tubles of kidney is valualble postmortem diagnostic methods for lead poisoning in dogs.

• Investigative Magnetic Resonance Imaging
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• v.16 no.2
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• pp.124-135
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• 2012

Purpose : The objective of this study was to investigate the differences of hippocampal volume and shape as well as the functional change between long life experienced taxi drivers and controls of Korean population. Materials and Methods: Three-dimensional T1-weighted images and blood oxygen level dependent functional MRI(fMRI) were obtained from 8 subjects, consisting of 4 experienced (20-30 years) taxi drivers and 4 age-matched controls. The hippocampal volume and shape were analyzed with three-dimensional T1-weighted images. In addition, neuronal activities of brain were analyzed using a blood oxygen level dependent fMRI between the two groups. Results: The hippocampal volume showed no statistically significant difference between the two groups (p > 0.05). The left hippocampi of the taxi drivers were slightly elongated with larger head and tail portions than those of the controls (p < 0.05, uncorrected). For the functional MRI, fusiform gyrus was specifically activated in taxi drivers, compared with the control group. Conclusion: The structural and functional changes of taxi driver's hippocampus indicate the functional differentiation as a result of occupational dependence on spatial navigation. In other words, the continuous usage of spatial navigation performance may diminish degeneration of hippocampus and the related brain regions.

• Journal of Acupuncture Research
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• v.29 no.5
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• pp.187-195
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• 2012

Objectives : Amyotrophic lateral sclerosis(ALS) is a progressive and incurable disease that causes degeneration of the motor neurons of the brain stem and spinal cord. The purpose of this study was to report the effectiveness of Sa-am acupuncture treatment on ALS patient. Methods : Following the stabilization period, a ALS patient respiratory figures(Et $C_{O2}$, Sp $_{O2}$, RR, pulse) were measured by using capnography & pulse oximetry for 30 minutes before acupuncture treatment. Acupuncture treatment such as lung tonification($SP_3(+){\cdot}LU_9(+){\cdot}HT_8(-){\cdot}LU_{10}(-)$), heart tonification($HT_9(+){\cdot}LR_1(+){\cdot}SI_8(-){\cdot}KI_{10}(-)$), liver tonification ($KI_{10}(+){\cdot}LR_8(+){\cdot}LU_8(-){\cdot}LR_4(-)$) were conducted for 5 days. Each Sa-am acupuncture treatment conducted at AM 7 : 00, AM 11 : 00, PM 4 : 30 of the day. During acupuncture treatment, the patient respiratory figures were measured equally for 30 minutes. The patient was treated by using Dong-bang acupuncture needles($0.30{\times}4.0$) and also stimulated using infra red. Results : The value of Et $C_{O2}$ has decreased more after Sa-am acupuncture lung tonification treatment than others. The value of pulse has decreased more after Sa-am acupuncture heart tonification treatment than others. The value of raspiration rate has decreased more after Sa-am acupuncture liver tonification treatment than others. And the value of Sp $O_2$ has increased more after Sa-am acupuncture liver tonification treatment than others. Conclusions : Although this study was subject to a few limitations, but it shows that Sa-am acupuncture treatment for ALS patients has a meaningful effect. This study needs to be developed further using a larger sample size to obtain more valuable and meaningful data.

• BMB Reports
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• v.47 no.10
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• pp.569-574
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• 2014

Heme oxygenase-1 (HO-1) degrades heme to carbon dioxide, biliverdin, and $Fe^{2+}$, which play important roles in various biochemical processes. In this study, we examined the protective function of HO-1 against oxidative stress in SH-SY5Y cells and in a Parkinson's disease mouse model. Western blot and fluorescence microscopy analysis demonstrated that PEP-1-HO-1, fused with a PEP-1 peptide can cross the cellular membranes of human neuroblastoma SH-SY5Y cells. In addition, the transduced PEP-1-HO-1 inhibited generation of reactive oxygen species (ROS) and cell death caused by 1-methyl-4-phenylpyridinium ion ($MPP^+$). In contrast, HO-1, which has no ability to transduce into SH-SY5Y cells, failed to reduce $MPP^+$-induced cellular toxicity and ROS production. Furthermore, intraperitoneal injected PEP-1-HO-1 crossed the blood-brain barrier in mouse brains. In a PD mouse model, PEP-1-HO-1 significantly protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity and dopaminergic neuronal death. Therefore, PEP-1-HO-1 could be a useful agent in treating oxidative stress induced ailments including PD.