Heung-Bin Lim;Hyung-Ok Sohn;Young-Gu Lee;Dong-Wook Lee
Journal of the Korean Society of Tobacco Science
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v.18
no.2
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pp.160-169
/
1996
Effect of cigarette smoke exposure on 1-methyl-4-phpnyl-1,2,3,6-tetrahydro-pyidine (Mm)-induced neurotoxicity was investigated in C57BL6 mice. Cigarette smoke exposure of mice to the mainstream smoke generated from 15 cigarettes for 10 mins per day, 5 days per week, for fi weeks, effectively attenuated the decline both in the level of striatal dopamine and the number of brrosine hydros:ylase-positive ceils in the brain caused by MPTP treahent. Exposure to cigarette smoke significantly decreased monoamine oxidate B activity in the cerebral cortex and cerebellum. The activity of brain antioxidant enzymes such as catalase, glutathione peroxidase, and Cu, Zn-superoxide dismutase, was not changed by cigarette smoke exposure or MPTP treatment. Sulfhydryl compounds content in all brain regions except for the striatum was uniquely increased by MPTP treatment, however, such an effect of MPTP was not observed in mice exposed to cigarette smoke. These results suggest that cigarette smoke exposure inhibits MPTP-induced neurotoxicity without influencing free radical metabolism in the brain of mice. This protective effect of cigarette smoke seems to be closely related with the decreased activity of brain monoamine oxidase H. Key words : cigarette smoke exposure, dopamine, monoamine oxidase B, antioxidant enzywles, MPTP.
Ryu, Sang Baek;Bae, Eun Kyung;Kim, Jinhyung;Hwang, Yong Sup;Im, Changkyun;Chang, Jin Woo;Shin, Hyung-Cheul;Kim, Kyung Hwan
The Korean Journal of Physiology and Pharmacology
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v.17
no.4
/
pp.299-306
/
2013
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely used as a treatment for the movement disturbances caused by Parkinson's disease (PD). Despite successful application of DBS, its mechanism of therapeutic effect is not clearly understood. Because PD results from the degeneration of dopamine neurons that affect the basal ganglia (BG) network, investigation of neuronal responses of BG neurons during STN DBS can provide informative insights for the understanding of the mechanism of therapeutic effect. However, it is difficult to observe neuronal activity during DBS because of large stimulation artifacts. Here, we report the observation of neuronal activities of the globus pallidus (GP) in normal and PD model rats during electrical stimulation of the STN. A custom artifact removal technique was devised to enable monitoring of neural activity during stimulation. We investigated how GP neurons responded to STN stimulation at various stimulation frequencies (10, 50, 90 and 130 Hz). It was observed that activities of GP neurons were modulated by stimulation frequency of the STN and significantly inhibited by high frequency stimulation above 50 Hz. These findings suggest that GP neuronal activity is effectively modulated by STN stimulation and strongly dependent on the frequency of stimulation.
Objectives : This study was purposed to the anti-oxidative effects of Polygonati Multiflori Caulis(henceforth PMC) on oxidized brain and liver cells in rats. Methods : After extraction of PMC with water, the water extract was divided into five fractions : hexane, ethyl ether, ethyl acetate, butanol and an aqueous fraction. The phenol contents of each fraction were measured. The lipid peroxidation inhibition effect were then investigated. Results : After processing PCM water and PCM fractionations on oxidized brain cells in rats, the SOD (super oxide dismutase) activity and glutathione content were increased, and the NO (nitric oxide) content was decreased. It had much higher SOD activity than liver cells in rats excluded in the n-BuOH and aqueous fractions. In case of oxidized liver cells in rats, the SOD activity and glutathione content increased, while both the NO content and the MDA (malondialdehyde) content decreased. It had much higher glutathione content than brain cells in rats in the every fractions. It had much lower MDA content than brain cells in rats in the Aqueous fractions and brain cells in rats had much lower MDA content than liver cells in rats in the total extract, n-hexane, EtOEt, EtOAc and n-BuOH fractions. Conclusions : PMC has anti-oxidative effect on oxidized liver cells and brain cells in rats, through there are differences in fraction. Additionally, Anti-oxidative effect of brain cells can be relaxed the mental nerve and it is related PMC effect.
In the present study, we tested whether lead intoxication could change the thiamine content and the activity of transketolase, one of thiamine-dependent enzymes, in the brain of rats. It was also tested whether administration of excessive thiamine can reverse the toxic manifestation of lead in the lead intoxicated rats. Four groups of Wistar rats were prepared: 1) control group, 2) lead treated group, 3) lead plus thiamine treated group and 4) thiamine deficient group. Each group of animals was divided into three subgroups based on ages: 3, 7 and 16 weeks. Lead concentration, thiamine content and the activity of transketolase in three different brain regions, i.e.,, telencephalon, brain stem and cerebellum, were measured in each group. Lead concentrations in brain regions of the lead treated group were significantly higher than those of the control group, and those of the lead plus thiamine treated group were significantly decreased from those of the lead treated group. Thiamine contents in the brain regions of the lead treated group were significantly lower than those of the control group, and those of the lead plus thiamine treated group were recovered back to those of the control group. Activities of transketolase in the brain regions of the lead treated group and the thiamine deficient group were significantly lower than those of the control group, while those of the lead plus thiamine treated group were higher than the lead treated group. The results from the present study suggest that neurotoxicity following lead intoxication in rats may be mediated, at least in part, through the changes of thiamine status and consequently thiamine-dependent biochemical reactions such as theactivity of transketolase.
In order to evalute the effects of radiation on mammalian neuronal system, we have examined the effect of gamma-ray radiation on the monoamine oxidase (MAO) activity in monoaminergic neurons. Following the whole body irradiation, MAO activity in the rat brain was measured as well as in the liver for the comparative studies between the neuronal and nonneuronal system. The effects of some radiation protectors and sensitizers were also examined in addition to the $O_2$ effect. The results can be summarized as follows. 1) The MAO activity of rat brain was minimally affected by the radiation dose up to 1,700 cGy Radiation dose above 2,500 cGy inhibited the brain MAO activity by no less than $l0\%.$ MAO-A form was found to be particularly sensitive to radiation. The liver MAO was somewhat inhibited (by about $5\%$) but hardly dependent on the dose of radiation. 2) The inhibitory effect on the brain was initiated immediately by the radiation dose of 2,500 cGy. On the contrary, for the liver, the inhibitory effect became apparent only 2 days after irradiation. 3) Two days after a dose of 2,500 cGy, Vmax and Km of the brain mitochondrial MAO decreased. For liver, Vmax decreased while Km increased, which indicates the kinetic patterns for the neuronal and nonneruronal systems are not affected similarly by radiation. 4) The effect of several known radiation protectors and sensitizers on MAO activity was tested ut no definite results were obtained. The level of -SH group increased in some degree upon radiation but not by the compounds. 5) MAO activity was not affected by $O_2$ concentration, while an elevated level of lipid peroxidase was found under the same condition. The results described here indicate that characteristics of MAO, one of the most important central nervous system enzymes, are liable to radiation, which is partially differentiated from the liver MAO. Also indicated are that the -SH groups are hardly related to the effect of radiation but the production of the lipid peroxide seems to be somewhat correlated to the effect of radiation.
Introduction: Many signal transduction pathways mediate cell's behavior by regulating expression level of involved genes. Abnormal behavior indicates loss of regulatory potential of pathways, and this can be attributed to loss of expression regulation of downstream genes. Therefore, function of pathways should be assessed by activity of a pathway itself and relative activity between a pathway and downstream genes, simultaneously. Results and Discussion: In this study, we suggested a new method to assess pathway's function by introducing concept of 'responsiveness'. The responsiveness was defined as a relative activity between a pathway itself and its downstream genes. The expression level of a downstream gene as a function of an upstream pathway activation characterizes disease status. In this aspect, by using the responsiveness we predicted potential progress in cancer development. We applied our method to predict primary and metastatic status of melanoma cancer. The result shows that the responsiveness-based approach achieves better performance than using gene or pathway information alone. The mean of ROC scores in the responsiveness-based approach was 0.90 for GSE7553 data set, increased more than 40% compared to a gene-based method. Moreover, identifying the abnormal regulatory patterns between pathway and its downstream genes provided more biologically interpretable information compared to gene or pathway based approaches.
Lee Young Chan;Choi Ho Seung;Lee Jun;Jeon Byung Hun
Journal of Physiology & Pathology in Korean Medicine
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v.18
no.6
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pp.1881-1891
/
2004
Daejowhan-gamibang(DJG) is used to prevention and treatment of cerebrovascular disease, heart disease, dementia, hyperlipdemia circulatory disturbance. Korean traditional herbal prescriptions and herb medicines in neuronal cells, which have been used for the treatment of stroke and brain diseases in Korean traditional medicine were screened to study the antioxidant effects and its mechanism. Daejowhan-gamibang water extract(DJGWE) was tested on their antioxidant activity using radical scavenging effects against ABTS. It showed significant antioxidant capacities at 50㎍ concentration. The antioxidant activity of DJGWE was determined in the different concentration (10㎍, 50 ㎍, and 100㎍). At the same time, the antiperoxidation effects was determined. Lipid peroxidation in brain homogenates induced by NADPH and ADP-Fe/sup 2+/ was significantly inhibited by DJGWE in vitro. DJGWE showed a potent antioxidant and antiperoxidative activity, further investigation, in vitro and in vivo, will be needed for the confirm of possibility as an antioxidant therapeutic agents and their optimal treatment of brain diseases in human. In searching the mechanism of antioxidant effects of DJGWE, it showed the inhibition of activity of JNK, p38, ERK and caspase 3 induced by hypoxia. So, DJGWE should be surveyed for the use of the potential therapeutic prescription for stroke and brain degenerative diseases such as pakinson's disease, dementia.
Kim, So-Ra;Park, Mi-Jung;Huh, Hoon;Lee, Heum-Sook;Kim, Young-Choong
YAKHAK HOEJI
/
v.38
no.4
/
pp.401-409
/
1994
The cholinergic activity of dammarane glycosides of Panax ginseng was examined both morphologically and chemically on primary cultures of chicken embryonic brain cells. When primary cultured chicken embryonic cells were treated with $50\;{\mu}g/ml$ of total dammarane glycosides of Panax ginseng followed by the exposure to 10mM atropine for 48 hr, lactate dehydrogenase levels within the cells remained at 36% of untreated control values while atropine-treated controls fell to 0% lactate dehydrogenase. It was found that cholinergic activity was mainly exerted by the panaxadiol glycosides. The treatment of the cells with $50\;{\mu}g/ml$ of panaxadiol glycosides followed by the exposure to atropine, lactate dehydrogenase levels within the cells remained at 60% of untreated control values. Ginsenoside $Rb_1$, a component of panaxadiol glycosides, was found to exert the cholinergic activity keeping the lactate dehydrogenase levels within the cells at 70% of untreated control values. The cholinergic activity of ginsenoside $Rb_1$ seems to be exerted through acting on the $Ca^{2+}$ channel in cultured brain cells.
The isozyme alteration of lactic dehydrogenase in the tissues of albino rat inhaled SO$_{2}$ were studied in vivo and in vitro, with the following results: (1) The H-type of LDH activity relatively dominated in the normal brain, heart and kidney tissues of rat, M-type in the normal lung, liver, and muscle tissues of the animal. (2) When rats inhale SO$_{2}$ in the concentration of 250 ppm, it appears that the M-type tends to predominate in the anaerobic tissues such as liver, kidney and muscle tissues and the H-type in the aerobic tissues such as brain and heart tissues. (3) When 5% SO$_{2}$ is introduced into tissue homogenates, LDH activities in the heart, lung, liver and muscle tissues are increased more than that of introducing room-air only. With sam treatment, LDH activity is decreased in the kidney tissue and no alteration is observed in the brain tissue. (4) Although, after the aeration of SO$_{2}$, the oxygen tension seems to bring decreases in the level of LDH activity in the anerobic tissues such as liver and muscle tissues, while, on the other hand, increases in the level of the activity in the aerobic tissues, such as the brain, heart and lung tissues. (5) Accordinglly, SO$_{2}$ affects LDH activities, its isozyme pattern of each organs, and their metabolic pathway by its absorption of the gas.
The effect of acute toluene exposure on behaviour and monoamine concentrations in the various brain regions were investigated in the rat. Toluene was adminstered via inhalation to rats at concentrations of 0, 1000, 10000, 40000 ppm for 20 min. During exposure to toluene, spontaneous locomotor activity was counted. After exposure, animals were sacrificed instantly and brains were separated. Regional concentratons of brain monoamines (norepinephrine, NE; dopamine, DA; 5- hydroxytryptamine, 5-HT) and its metabolites (3,4-dihydroxyphenylacetic acid, DOPAC; homovanillic acid, HVA; 5-hydroxyindole-3-acetic acid, 5-HIAA) were determined. The changes in locomotor activity during toluene exposure depended on the toluene concentration. At 1000 ppm concentration, spontaneous locomotor activity increased initially and thereafter decreased. At higher concentrations (10000 ppm and 40000 ppm), spontaneous locomotor activity decreased and eventually ceased. A regional analysis of VA, NE, 5-HT, VOPAC, HVA, and 5-HIAA indicated a significant decrease in VA concentrations in cerebellum and striatum while NE and 5-HT concentrations were significantly increased in the cerebellum and cortex. 5-HIAA concentrations were significantly increased in all brain regions. DOPAC concentrations were significantly increased in cerebellum and cortex while decreased in striatum. These results especially indicated that metabolic conversion of DA to HVA in striatum was highly increased by toluene inhalation. However, It remains to elucidate between behavioural responses and monoamine changes.
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