• 대한수의학회지
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• 제42권3호
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• pp.429-436
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• 2002

Hydrocepbalus may be an acquired or a congenital condition. We have studied the macroscopic and microscopic changes in the hydrocephalus of an inbred Sprague-Dawley rat at postnatal week 8. The animal suspected with the hydrocephalus showed clinical syndromes such as depression, severe ataxia, eye abnormalities, dome-shaped head, and persistent fontanelle. With the postmortem examination, the suspected animal was clearly revealed as a severe internal hydrocephalus. In this animal, severe ventriculomegaly was limited to the third and lateral ventricles, and cortical thining was most apparent in the parieto-occipital region. With the routine histological examination, brain tissue showed aqueductal obstruction, thinning of the cerebral cortex, severe ependymal damage, subependymal edema, damage of choroid plexus of fourth ventricle, enlarged cortical vessels, and expanded ventricles. Aqueductal obstruction was observed with the appearance of simple stenosis at the level of rostral colliculus. Subsequently, the other structures of brain such as septal nucleus, caudate nucleus, and hippocampus etc. were abnormally reconstructed by hydrocephalus. This study suggests that the hydrocephalus can be taken place by primary aqueductal obstruction and this type of hydrocephalus is classified as uncommunicating type. Though the mechanism of aqueductal obstruction is not clear, the morphological studies of this case may be helpful for the further study of hydrocephalus.

• The Korean Journal of Physiology and Pharmacology
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• 제1권2호
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• pp.117-125
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• 1997

The N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic neurotransmission is involved in synaptic plasticity, developmental processes, learning and memory and many neuropathological disorders including age-related diseases. In the present study, regulation of the NMDA receptor properties by various ligands was investigated using $[^3H]MK-801$ binding studies in the synaptic membranes of young and aged rat forebrains. The binding in the presence of glutamate and glycine increased dramatically with growth between 1 and 6 weeks old, and thereafter declined gradually with aging. Glutamate, glycine or spermine respectively increased the binding with growth. Glutamate maintained the binding during aging, while glycine or spermine significantly decreased the binding in the aged brain. The maximum stimulation by glycine varied depending on the ages of brains. Greater sensitivity to glycine was observed at 1 week and 3 months and the sensitivity was significantly reduced in the aged brain. In contrast, spermine showed similar stimulation patterns in young and aged rats. These results indicated that the functional properties of the NMDA receptor-ion channel complex in young and aged rat forebrains are differentially regulated by agonists, and the reduction of the receptor function with normal aging may be, in some degree, due to the reduction of the receptor sensitivity to glycine.

• Toxicological Research
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• 제23권4호
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• pp.311-319
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• 2007

Elevated blood levels of homocysteine (a sulfur-containing amino acid) have been linked to increased risk of cerebrovascular disease including Alzheimer's disease. A recent study suggests that elevated homocysteine levels may lead to replicative senescence in vitro called 'permanent arrest of cell cycle' caused by oxidative stress. In this study, serum homocysteine level in rat was reduced by Lentinus edodes-powder diet, resulting in the reduced level of oxidative stress in rat brain. In addition, homocysteine-induced replicative senescence treated with or without Lentinus edodes-powder was analyzed by population doubling in vitro. The Lentinus edodes-powder induced a increased number of population doubling in primary neuron cell isolated from rat-cerebral cortex. This indicates that Lentinus edodes-powder would delay a homocysteine-induced aging of neuron cells in brain, showing a possible role in preventing cerebrovascular diseases including Alzheimer's disease.

• 대한의생명과학회지
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• 제16권2호
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• pp.96-104
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• 2010

In this study, the effects of HP4060, a pomegranate extract, on Sprague-Dawley (SD) female rats were investigated. SD rats used in the experiment were divided into 3 groups: a control group, 100 mg HP4060/kg rat powder fed group, and 25 mg HP4060/kg rat liquid fed group. After 20 days of administration, the changes of the brain neurotransmitters were measured. The data showed that the concentration of the serotonin and the norepinephrine were increased, whereas that of the epinephrine was decreased in HP4060 administered groups. In addition, the improving effect of HP4060 on depression symptom of menopause women were shown by increased immobility time of the SD rates in a separate experiment. The uterus weight of HP4060 fed groups were also shown to be increased. In order to monitor toxic effect of HP4060, glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels were measured, and the results showed that no significant difference in GOT and GPT levels among experimental groups implying no significant toxic side effects of HP4060. According to these results, it seems clear that HP4060 may improve symptoms of hot flush and depression caused by menopause without significant level of toxic effects.

• Nutritional Sciences
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• 제8권4호
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• pp.231-236
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• 2005

This study investigated the changes in the neuronal nitric oxide synthase (nNOS) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activities during food restriction in the rat brain such as cerebral cortex, cerebellum, caudate pautamen and hypothalamus. The rats were placed on a restricted feeding schedule consisting of half the ad libitum quantity for 3 days and 1, 2, 4, 6 and 9 weeks, and a free feeding schedule for 4 weeks. The loss of body weight peaked after 1 week of food restriction and persisted during the entire 9-week period of food restriction. The dramatic weight change in the first week ($12\%$) and the reduction in weight changes thereafter suggest that major adaptation changes occur early and body maintenance occurs subsequently. In the hypothalamus, the optical densities of the NADPH-d and nNOS immunoreactivities were found to be significantly higher in the 1-week and lower in the 9-week food restricted group than in the ad libitum fed control rats. In contrast, in the cerebral cortex, the optical densities of the NADPH-d- and nNOS-positive neurons were not changed significantly during the period of food restriction. This study provides the morphological evidence showing that food restriction has a significant effect on the nitric oxide synthesizing system of the hypothalamus.

• The Korean Journal of Physiology and Pharmacology
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• 제1권2호
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• pp.127-133
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• 1997

Lithium remains the most widely used therapeutic agent for bipolar affective disorder, particularly mania. Although many investigators have studied the effects of lithium on abnormalities in monoamine neuro-transmitter as a pathophysiological basis of affective disorder, the action mechanism of lithium ion remains still unknown. To explore the action mechanism of lithium in the brain, we examined the effects of lithium on the extrasynaptosomal concentrations of catecholamines and their metabolites. Synaptosomes were prepared from the rat forebrains and assays of catecholamines and metabolites were made using HPLC with an electrochemical detector. Lithium of 1mM decreased the extrasynaptosomal concentrations of NE from the control group of $3.07{\pm}1.19$ to the treated group of $0.00{\pm}0.00$ (ng/ml of synaptosomal suspension) but not that of DHPG. It can be suggested that lithium increases synaptosomal uptake of NE. Increased intraneuronal uptake of NE would decrease neurotransmission and extraneuronal metabolism of NE. Because increased brain NE metabolism and neurotransmission have been suggested as important components in the pathophysiology of bipolar affective disorder, especially mania, lithium-induced increase of intraneuronal NE uptake can be suspected as an action mechanism of therapeutic effect of lithium in manic patient, possibly in bipolar affective disorder.

• 약학회지
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• 제34권5호
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• pp.311-322
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• 1990

This study primarily attempted to investigate the effects of methamphetamine on stereotyped behavior. Furthermore, an extensive experiment was conducted to examine the cortex methamphetamine concentration and levels of dopamine, serotonin, and their metabolites in striatum, septum and hypothalamus. Following treatment with 10 mg/kg methamphetamine, stereotyped behavior was observed in 10 minutes. Consequently female rats displayed more intense and longer lasting activity than the male. The concentration of cortex methamphetamine was even higher in female than male. The administration of methamphetamine increased the rate of dopamine turnover-i.e. lower dopamine, higher homovanillic acid in the striatum, septum. The highest rate was found in the striatum. Methamphetamine decreased the levels of serotonin, and its metabolite of 5-indoleacetic acid in the striatum, septum. An intensity in behavioral response was accompanied by an increase in dopamine turnover, a decrease in serotonergic transmission. The reduction of 3,4-dihydroxyphenylacetic acid-i.e. the metabolite of dopamine was due not to the inhibition of monoamine oxidase but to the induction of monoamine oxidase but to the induction of catechol-O-methyltransferase. The phenomenon of biogenic amines by methamphetamine concurred upon the concentration of methamphetamine in the brain. This process preceded stereotyped behavior. After single injection of 10 mg/kg methamphetamine, the levels of biogenic amines recovered within 6 hours.

• Toxicological Research
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• 제13권3호
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• pp.251-256
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• 1997

Toluene inhalation increases glutamate level and its receptor in various brain regions. In this study, nitric oxide synthase (NOS) activities were investigated in various rat brain regions using NADPH diaphorase staining method which examined histochemical changes of NOS in the neural cells. Also, in vitro LDH leakage assay and MTT test were performed to investigate the toxic influences of toluene in cultured granule cell of rat cerebellum which was significantly affected with toluene in vivo. Rats were exposed to toluene of 10000 ppm for 3 days. 7 days and 14 days by 20 min $\times$ 2 times a day. NADPH diaphorase staining was processed in the different brain regions after inhalation. NADPH diaphorase staining density was not significantly changed at 3 days inhalation group, but the density decreased in proportion to the duration of toluene inhalation. Over 30% of staining density was decreased at 14 days group which was maximum duration of inhalation in this study. The tendency of staining density decrease was significant in granule cell of cerebellum. Cell death by toluene exposure was observed in cultured cerebellar granule cell. $EC_{50}$ measured with LDH leakage assay and MTT test were 43 mM and 72 mM respectively.

• Biomolecules & Therapeutics
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• 제9권2호
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• pp.88-95
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• 2001

(+)-Methamphetamine (METH) is a psychostimulant, which has been the most popular abused drug in Korea. The rewarding mechanism in METH abuse has been reported to be mediated by dopaminergic system. Recently, it has been reported that dopamine releaser (phentermine) plays a dominant role in the discriminative stimulus effects of METH, whereas 5-HT releaser (fenfluramine) can strongly modify METH self-administration. The present study is designed to assess the behavioral changes and the changes of the serotonin receptors in the brains of rats administered repeated of self-administered METH. The repeated administration of 1.0 mg/kg/day METH for 12 days increased locomotor activities, and there was no difference between i.v. and i.p. treatment. Rats had actively acquired METH self-administration for 3 weeks at 0.1 or 0.2 mg/kg/injection. Whereas, it was taken few days to acquire sucrose pellet self-administration. The binding of [$^3$H]-8-hydroxy-DPAT (5-H $T_{1A}$ receptors) and [$^3$H]-5-carboxytryptamine (5-H $T_{1B}$ receptors) to brain sections was examined. Both passive administration and self-administration of METH did not change significantly the serotonin receptors levels in hippocampus, striatum and nucleus accumbens. These results suggest that serotonin receptors may not change in the acquisition period of METH self-administration, and we are trying to investigate the serotonin receptors levels of brain in rats maintained of METH self-administration.n.n.

• Journal of Preventive Medicine and Public Health
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• 제16권1호
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• pp.79-88
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• 1983

There has been some evidence concerning the fact that trihalomethanes(THMs), toxic chlorinated compounds, may be present in drinking water. One of the important methodologies to evaluate the toxicity of THMs is to determine enzyme alteration in experimental animal tissues after treatment. This study was intended to investigate how lactic dehydrogenase(LDH) of rat tissues is affected by administration of chloroform($CHCl_3$) and dichloromonobromomethane($CHCl_2\;Br$). THMs, high dose(1/10 LD50) or low dose(1/50 LD50) of $CHCl_3$ or $CHCl_{2}Br$ were administered orally to experimental rats for 4 or 8 weeks. The treated groups of rats were sacrificed to determine LDH specific activity and isozyme pattern in various organs which were liver, thigh muscle, kidney and brain. The conclusions were obtained as follows: 1. Alteration of LDH activities and isozyme patterns were revealed before morphologic changes in tissues. 2. The LDH specific activities were increased significantly in liver and brain after administration of high concentrations of $CHCl_3$ and $CHCl_{2}Br$ for 4 weeks respectively. Otherwise, they were decreased significantly in liver, muscle and kidney after administration for 8 weeks. 3. The isozyme activities of LDH-4 and LDH-5 were increased in muscle, brain, and especially the liver. 4. It was more distinct for the decrement of LDH H-type isozyme than the increment of M-type isozyme in muscle.