• Molecules and Cells
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• v.45 no.9
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• pp.640-648
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• 2022

CD133, also known as prominin-1, was first identified as a biomarker of mammalian cancer and neural stem cells. Previous studies have shown that the prominin-like (promL) gene, an orthologue of mammalian CD133 in Drosophila, plays a role in glucose and lipid metabolism, body growth, and longevity. Because locomotion is required for food sourcing and ultimately the regulation of metabolism, we examined the function of promL in Drosophila locomotion. Both promL mutants and pan-neuronal promL inhibition flies displayed reduced spontaneous locomotor activity. As dopamine is known to modulate locomotion, we also examined the effects of promL inhibition on the dopamine concentration and mRNA expression levels of tyrosine hydroxylase (TH) and DOPA decarboxylase (Ddc), the enzymes responsible for dopamine biosynthesis, in the heads of flies. Compared with those in control flies, the levels of dopamine and the mRNAs encoding TH and Ddc were lower in promL mutant and pan-neuronal promL inhibition flies. In addition, an immunostaining analysis revealed that, compared with control flies, promL mutant and pan-neuronal promL inhibition flies had lower levels of the TH protein in protocerebral anterior medial (PAM) neurons, a subset of dopaminergic neurons. Inhibition of promL in these PAM neurons reduced the locomotor activity of the flies. Overall, these findings indicate that promL expressed in PAM dopaminergic neurons regulates locomotion by controlling dopamine synthesis in Drosophila.

• Archives of Pharmacal Research
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• v.17 no.6
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• pp.398-404
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• 1994

The behavioral response, depamine metabolism, and characteristics of dopamine subtypes after developing the hyperlycemia were studied in the striata of rats. In animals developed hyperglycemia, the on-set duration of cataleptic behavior responded to SCH 23390 injection was delayed abd shortened, respectively. However, the cataleptic response to spiperone occurred significantly earlier in on-set and prolonged in duration. Dopamine metabolites, dihydroxyphenylacetic acid (DDPAC) and homovanillic acid (HVA), were significantly reduced in teh striata of hyeprglycemic rats. However, level of DA was significantly increased. It is noted that the ratios of DOPAC and HVA to DA were decreased, suggesting decreased tumover of DA. The affinity of striatal D-1 receptors was significantly increased without changes in the number of binding sites, while the maximum binding number of D-2 recptors was significantly increased without affecting its affinity in the diabetic rats. These results indicate that the dopaminergic activity in striatia was altered in hyperglycemic rats. Furthermore, it suggests that the upregulation of dopamine receptors might be due to the decreased dopamine matabolism.

• Archives of Pharmacal Research
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• v.18 no.4
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• pp.249-255
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• 1995

The changes in the levels of the extracellular dopamine metabolites and the responses to various dopamine agents were studied by using microdialysis inhyperglycemic rat striatum. The hyperglycemia were induced by the administriation of streptozotocin (40 mg/kg, i.p. for 3 days.). The basal levels of striatal dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were significantly decreased in hyperglycemic rat striatum. After the administration ofl D-1 and D-2 receptor antagonists, SCH-23390 and (-)sulpiride, to rats 14 days after the last administration of STZ, the increased rates in DOPAC levels were higher in hyper- than in normoglycemic rats. However, after the administration of dopamine autoeceptor agonist, 3(-)PPP, the levels of the extracellular HVA were increased in normoglycemic rats, but those were not altered in hyperglycemic rats. The results indicate that the striatal dopamine activities were decreased in the hyperglycemic rats and suggest that release of dopamine may be decreased in hyperglycemic rats. Furthermore it suggest that the increase in the levels of the extracellular dopamine metabolites by dopamine antagonists might be dur to the incrrased sensitivities of the dopamine receptors in hyperglycemic state.

• Korean Journal of Biological Psychiatry
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• v.3 no.1
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• pp.51-56
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• 1996

The effects of 3 week treatment with haloperidol(2mg/kg/day, i.p.) on dopamine(DA) D2 receptor and DA metabolism in rat striata were studied at various time points after withdrawal from the drug treatment. Striatal DA D2 receptors were characterized with the radioligand 0.5nM [$^3H$]Spiperone. Dopamine(DA), homovanillic acid(HVA), 3,4-dihydroxyphenyl acetic acid(DOPAC) in rat striatum were measured with the high performance liquid chromatography. Drug withdrawal for 1 week induced significant increase in the number of D2 receptor in striatum after withdrawal for 1 week(p<0.05), and then this change was restored to control level during the withdrawal time of 2 and 4 weeks. There was no difference in striatal concentrations of DA and its metabolites among the groups. In conclusion, one-week withdrawal from chronic haloperidol treatment induced DA D2 receptor supersensitivity in the striatum, and that was normalized rapidly. Though this adaptive change in DA receptors, it may not affect the metabolism of DA in striatum.

• The Korean Journal of Pharmacology
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• v.27 no.1
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• pp.7-12
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• 1991

We measured the developmental increase of tyrosine hydroxylase(TH) activity and dopamine content with high performance liquid chromatography with electrochemical detection(HPLC-EC) in dissociated cultures of fetal rat brainstem(E14). TH activity and dopamine content increased progressively upto 7 days in vitro, when the effects of various drugs on the dopamine contents were studied. ${\alpha}-Methyl-p-tyrosine$, a TH inhibitor and NSD-1015, an inhibitor of aromatic amiono acid decarboxylase effectively depleted dopamine contents. Dopamine contents were depleted by reserpine and increased by pargyline. When cultures grown for 1 week in control medium were then exposed to tetrodotoxin$(0.1\;{\mu}M$) for 7 days, exposure to tetrodotoxin markedly decreased TH activity. All the above results indicate that dopamine metabolism in the cultered cells reflect reliably the property of brain dopamine metabolism. We suggest that measuring TH activity and dopamine content in brainstem culture with HPLC-EC can be useful tool in the study of pharmacology as well as toxicology of the central dopaminergic system.

• Toxicological Research
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• v.30 no.4
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• pp.267-276
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• 2014

Exposures to lead (Pb) are associated with neurological problems including psychiatric disorders and impaired learning and memory. Pb can be absorbed by iron transporters, which are up-regulated in hereditary hemochromatosis, an iron overload disorder in which increased iron deposition in various parenchymal organs promote metal-induced oxidative damage. While dysfunction in HFE (High Fe) gene is the major cause of hemochromatosis, the transport and toxicity of Pb in Hfe-related hemochromatosis are largely unknown. To elucidate the relationship between HFE gene dysfunction and Pb absorption, H67D knock-in Hfe-mutant and wild-type mice were given drinking water containing Pb 1.6 mg/ml ad libitum for 6 weeks and examined for behavioral phenotypes using the nestlet-shredding and marble-burying tests. Latency to nestlet-shredding in Pb-treated wild-type mice was prolonged compared with non-exposed wild-types (p < 0.001), whereas Pb exposure did not alter shredding latency in Hfe-mutant mice. In the marble-burying test, Hfe-mutant mice showed an increased number of marbles buried compared with wild-type mice (p = 0.002), indicating more repetitive behavior upon Hfe mutation. Importantly, Pb-exposed wild-type mice buried more marbles than non-exposed wild-types, whereas the number of marbles buried by Hfe-mutant mice did not change whether or not exposed to Pb. These results suggest that Hfe mutation could normalize Pb-induced behavioral alteration. To explore the mechanism of repetitive behavior caused by Pb, western blot analysis was conducted for proteins involved in brain dopamine metabolism. The levels of tyrosine hydroxylase and dopamine transporter increased upon Pb exposure in both genotypes, whereas Hfe-mutant mice displayed down-regulation of the dopamine transporter and dopamine D1 receptor with D2 receptor elevated. Taken together, our data support the idea that both Pb exposure and Hfe mutation increase repetitive behavior in mice and further suggest that these behavioral changes could be associated with altered dopaminergic neurotransmission, providing a therapeutic basis for psychiatric disorders caused by Pb toxicity.

• YAKHAK HOEJI
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• v.43 no.1
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• pp.33-41
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• 1999

Whereas as selective inhibitor of monoamine oxidase type B, ${\ell}-deprenyl$ (selegiline), is now widely used in the treatment of Parkinson's disease, the precise action mechanism of the drug remains elusive. In this study, to investigate protective effect of ${\ell}-deprenyl$ against the dopamine depletion induced by 6-hydroxydopamine (6-OHDA), the changes in tissue contents of dopamine, serotonine (5-HT) and their metabolites by ${\ell}-deprenyl$ were examined in intact and 6-OHDA-lesioned rat brain. In intact rats, a single intraperitoneal (i.p.) administration of ${\ell}-deprenyl$ showed a no change in striatal dopamine and its metabolites at low concentrations (0.25 and 1 mg/kg), but significantly inhibited dopamine metabolism at a higher concentration (10 mg/kg). The repeated administration of ${\ell}-deprenyl$ (0.25 and 1 mg/kg, i.p., for 21 consecutive days) reduced the contents of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in dose-dependent manners without changes in dopamine content. Bilateral intracerebroventricular (i.c.v) infusion of 6-OHDA ($100{\;}\mu\textrm{g}/10{\;}{\mu}{\ell}/hemisphere$) depleted dopamine in striatum and septum by 81% and 90% respectively. When rats were pretreated with ${\ell}-deprenyl$ before 6-OHDA administration, the striatal and septal dopamine levels were significantly increased by about 3.0-fold and 3.4-fold, respectively, compared to the untreated 6-OHDA-lesioned rat. Pretreatment of ${\ell}-deprenyl$ also significantly enhanced the dopmaine metabolites, DOPAC, HVA and 3-methoxytyramine, in the striatum, and DOPAC in the septum. These results indicate that a ${\ell}-deprenyl$ pretreatment prevents 6-OHDA-induced depletion of striatal dopamine and its metabolites.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.11-18
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• 1992

Rats were treated with physostigmine, using 0.75 mg/kg acutely, with 0.75 mg/kg daily for 7 dats, or with 0.15 mg/kg/h continuously for 7 days. Striatal dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels and tyrosine hydroxylase (TH) activities were studied. After acute treatment striatal DOPAC and HVA concentrations were significantly increased without changes in DA level 1 h, but not 24 h. And also the ratios of DOPAC/DA and HVA/DA were increased, suggesting an increased turnover of DA. however TH activities were decreased 24h, but not 1h after acute administration. After both daily and continuous treatment with physostigmine for 7 days, neither DA nor its metabolites were changed. However their ratios were decreased, suggesting a decreased turnover of DA. The TH activities were only decreased in the daily treated group, but not in the continously treated one. These results indicate that dopamine metabolisms are changed after acute and subacute administration with physostigmine. Further it suggest that the subacute stimulation of cholinergic activity may induce the dopamine metablism and activity to be decreased.

• Clinical and Experimental Pediatrics
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• v.46 no.8
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• pp.789-794
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• 2003

Purpose : We intended to evaluate the effect of hypoxia-ischemia on extracellular striatal monoamine metabolism in neonatal rat brains by in vivo microdialysis. Methods : The right common carotid arteries of five or six-day old rats were surgically ligated, and the probes for microdialysis were inserted into the right striatum with stereotaxic instrument. After stabilization for two hours, artificial cerebrospinal fluid was infused via the probe for microdialysis and samples were collected during hypoxia-ischemia and recovery periods at 20 minute intervals. The concentrations of DA(dopamine), DOPAC(3,4-di-hydroxyphenyl acetic acid), HVA(homovanillic acid), NE(norepinephrine), and 5-HIAA(5-hydroxy indole-acetic acid) were measured by HPLC(high performance liquid chromatography) and the changes were analysed. Results : The striatal levels of dopamine metabolites such as DOPAC and HVA, were significantly decreased during hypoxia-ischemia, and increased to their basal level during reoxygenation(P<0.05). Dopamine mostly increased during hypoxia but statistically not significant(P>0.05). DOPAC showed the most remarkable decrease($23.0{\pm}4.2%$, P<0.05), during hypoxia-ischemia and increase to the basal levels during reoxygenation($120.8{\pm}54.9%$, P<0.05), and HVA showed the same pattern of changes as those of DOPAC during hypoxia-ischemia($35.3{\pm}7.6%$ of basal level, P<0.05) and reoxygenation ($105.8{\pm}32.3%$). However, the level of NE did not show significant changes during hypoxia-ischemia and reoxygenation. The levels of 5-HIAA decreased($74.9{\pm}3.1%$) and increased($118.1{\pm}7.8%$) during hypoxia-ischemia and reoxygenation, respectively(P<0.005). Conclusion : Hypoxia-ischemia had a significant influence on the metabolism of striatal monoamine in neonatal rat brains. These findings suggest that monoamine, especially dopamine, and its metabolites could have a significant role in the pathogenesis of hypoxic-ischemic injury of neonatal rat brains.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.141-151
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• 2007

Parkinson's disease is one of the most frequent neurodegenerative diseases, which mainly affects the elderly. Parkinson's disease is often difficult to differentiate from atypical parkinson diorder such as progressive supranuclear palsy, multiple system atrophy, dementia with Lewy body, and corticobasal ganglionic degeneration, based on the clinical findings because of the similarity of phenotypes and lack of diagnostic markers. The accurate diagnosis of Parkinson's disease and atypical Parkinson disorders is not only important for deciding on treatment regimens and providing prognosis, but also it is critical for studies designed to investigate etiology and pathogenesis of parkinsonism and to develop new therapeutic strategies. Although degeneration of the nigrostriatal dopamine system results in marked loss of striatal dopamine content in most of the diseases causing parkinsonism, pathologic studies revealed different topographies of the neuronal cell loss in Parkisonism. Since the regional cerebral glucose metabolism is a marker of integrated local synaptic activity and as such is sensitive to both direct neuronal/synaptic damage and secondary functional disruption at synapses distant from the primary site of pathology, an assessment of the regional cerebral glucose metabolism with F-18 FDG PET is useful in the differential diagnosis of parkinsonism and evaluating the pathophysiology of parkisonism.