Biomedical subjects

Younjoo Park

Publications and source records attributed to Younjoo Park.

9 recordsLinked to original sources

PubMed2005

Butorphanol dependence increases hippocampal kappa-opioid receptor gene expression.

Butorphanol is a synthetic opioid agonist/antagonist analgesic agent, which exerts its effects mainly via kappa-opioid receptors. Characterizations of the gene expression levels of the mRNA for and protein levels of the kappa-opioid receptor in different brain regions of rats are essential for investigating possible mechanisms in the development of physical dependence on and withdrawal from butorphanol. Animals were rendered dependent by intracerebroventricular (i.c.v.) infusion of butorphanol (26 nmol/microl/hr) via osmotic minipumps for 3 days. Rats were sacrificed immediately (dependent group) or 7 hr after discontinuation of i.c.v. butorphanol infusion (withdrawal group). Expression levels of the mRNA for the kappa-opioid receptor, as detected by reverse transcription-polymerase chain reaction followed by Southern blot analysis, were significantly increased in the cerebral cortex, striatum, and midbrain, including thalamus, hippocampus, and pons, in animals dependent on butorphanol. In both dependent and withdrawal groups, Western blot analysis of kappa-opioid receptor protein levels showed significant increases in the amygdaloid nucleus, paraventricular thalamus, and thalamus. However, in the withdrawal group, there were significant decreases in the hippocampus and cortical regions, including the frontal, parietal, and temporal cortex. Regional changes in the mRNA for and protein levels of the kappa-opioid receptor focus attention on highly special roles for this receptor in the development of physical dependence on and the expression of withdrawal from butorphanol dependence.

Animals↗

PubMed2004

3-monochloropropane-1,2-diol does not cause neurotoxicity in vitro or neurobehavioral deficits in rats.

3-monochloro-1,2-propanediol (3-MCPD) is a contaminant of acid-hydrolyzed vegetable protein. Several reports have suggested that chronic exposure to 3-MCPD could produce neurotoxicity in vitro or neurobehavioral effects in experimental animals. The present study further explored the in vitro neurotoxic effects of 0.1-100 microM 3-MCPD on PC12 and N18D3 cell lines. In addition, to investigate the effects of repeated ingestion of 3-MCPD on neurobehavioral impairments parameters in rats, motor activity, landing foot splay, and grip strength tests were performed, following treatment with 3-MCPD at dose levels of 10, 20, and 30 mg/kg per day for 11 weeks. We demonstrated that no significant neurotoxic effects were present in 3-MCPD-treated rats compared to saline-treated control rats, whereas, acrylamide, used as a positive control, induced significant deficits in all neurobehavioral parameters in both male and female rats. On the other hand, body weight gain was significantly decreased in high dose 3-MCPD-treated male rats as well as in acrylamide-treated rats. Taken together, these results suggest that 3-MCPD, at the dose levels used for this study, does not produce in vitro neurotoxicity or neuromotor deficits in vivo.

Animals↗

PubMed2004

The effect of PARP inhibitor on ischaemic cell death, its related inflammation and survival signals.

Poly(ADP-ribose) polymerase (PARP) plays an important role in ischaemic cell death, and 3-aminobenzamide (3-AB), one of the PARP inhibitors, has a protective effect on ischaemic stroke. We investigated the neuroprotective mechanisms of 3-AB in ischaemic stroke. The occlusion of middle cerebral artery (MCA) was made in 170 Sprague-Dawley rats, and reperfusion was performed 2 h after the occlusion. Another 10 Sprague-Dawley rats were used for sham operation. 3-AB was administered to 85 rats 10 min before the occlusion [3-AB group (n = 85) vs. control group without 3-AB (n = 85)]. Infarct volume and water content were measured, brain magnetic resonance imaging, terminal deoxynucleotidyltransferase (TdT)-mediated dUTP-biotin nick end-labelling (TUNEL) and Cresyl violet staining were performed, and immunoreactivities (IRs) of poly(ADP-ribose) polymer (PAR), cleaved caspase-3, CD11b, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), phospho-Akt (pAkt) and phospho-glycogen synthase kinase-3 (pGSK-3) were compared in the peri-infarcted region of the 3-AB group and its corresponding ischaemic region of the control group at 2, 8, 24 and 72 h after the occlusion. In the 3-AB group, the infarct volume and the water content were decreased (about 45% and 3.6%, respectively, at 24 h), the number of TUNEL-positive cells was decreased (about 36% at 24 h), and the IRs of PAR, cleaved caspase-3, CD11b, ICAM-1 and COX-2 were significantly reduced, while the IRs of pAkt and pGSK-3 were increased. These results suggest that 3-AB treatment could reduce the infarct volume by reducing ischaemic cell death, its related inflammation and increasing survival signals. The inhibition of PARP could be another potential neuroprotective strategy in ischaemic stroke.

Animals↗

PubMed2003

Epigallocatechin gallate protects nerve growth factor differentiated PC12 cells from oxidative-radical-stress-induced apoptosis through its effect on phosphoinositide 3-kinase/Akt and glycogen synthase kinase-3.

The effects of epigallocatechin gallate (EGCG) on the phosphoinositide 3-kinase (PI3K)/Akt and glycogen synthase kinase-3 (GSK-3) pathway during oxidative-stress-induced injury were studied using H2O2-treated PC12 cells, which were differentiated by nerve growth factor (NGF). Following 100 microM H2O2 exposure, the viability of differentiated PC12 cells (EGCG or z-VAD-fmk pretreated vs. not pretreated) was evaluated the number of viable cell with Trypan blue and 3,4,5-dimethylthiazol-2-yl (MTT). Additionally, expression of cytochrome c, caspase-3, poly(ADP-ribose) polymerase (PARP), PI3K/Akt and GSK-3 was examined using Western blot analyses. EGCG or z-VAD-fmk-pretreated PC12 cells showed an increase of viability compared to untreated PC12 cells, and pretreatment of PC12 cells with either agent induced a dose-dependent inhibition of caspase-3 activation and PARP cleavage. However, inhibition of cytochrome c release was only detected in EGCG-pretreated cells. Upon examination of the PI3K/Akt and GSK-3 upstream pathway, Western blots of EGCG pretreated cells showed decreased immunoreactivity (IR) of Akt and GSK-3 and increased IR of p85a PI3K, phosphorylated Akt and phosphorylated GSK-3. In contrast, no changes were seen in z-VAD-fmk-pretreated cells. These results show that EGCG affects the PI3K/Akt, GSK-3 pathway as well as downstream signaling, including the cytochrome c and caspase-3 pathways. Therefore, it is suggested that EGCG-mediated activation of PI3K/Akt and inhibition of GSK-3 could be a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury.

Animals↗

PubMed2003

Increased dopamine D2 receptor binding and enhanced apomorphine-induced locomotor activity in mu-opioid receptor knockout mice.

Previous studies from our laboratory have indicated possible interactions between opioidergic and dopaminergic neurons in the central nervous system. In this study, apomorphine-induced locomotor activity and the D1 and D2 subtype dopamine receptor binding were examined in mice lacking the mu-opioid receptor genes. The ambulatory time, vertical time and total motor distance of locomotor activity were measured after administration of apomorphine (2mg/kg, i.p.) for a period of 90min. The autoradiographic studies of D1 and D2 dopamine receptors were conducted using [3H] SCH23390 and [3H] raclopride as ligand, respectively. In wild type mice that received apomorphine, 2mg/kg, i.p., the locomotor activity such as ambulatory time, vertical time and total motor distance were not significantly altered as compared with that of the saline control group. However, the locomotor activity measured was significantly increased in the same dose of apomorphine treated mu-opioid receptor knockout mice between 5 and 40min after administration. The results obtained also show that the binding of D2 dopamine receptor in mu-opioid receptor knockout mice was significantly higher than that of the wild type in the caudate putamen. However, the binding of the D1 dopamine receptor in mu-opioid receptor knockout mice was not significantly different from that of the wild type. It appears that the apomorphine treated mu-opioid receptor knockout mice showed enhancement in locomotor activity. The enhanced locomotor activity may be related to the compensatory up-regulation of D2 dopamine receptors in mice lacking mu-opioid receptor genes.

Analysis of Variance↗

PubMed2003

Enhanced binding of nor-binaltorphimine to kappa-opioid receptors in rats dependent on butorphanol.

Autoradiographic characterization of binding for brain kappa(1) ([(3)H]CI-977) and kappa(2) ([(3)H]bremazocine) in the presence of DAMGO ([D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin), DPDPE ([D-Pen(2), D-Pen(5)]-enkephalin), and U-69,593 opioid receptors, in the presence of different concentrations of a selective unlabeled kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI), was performed in rats in which dependence on or withdrawal from butorphanol had been established. Dependence was induced by a 72 hr intracerebroventricular (i.c.v.) infusion with butorphanol (26 nmol/microl/hr; butorphanol dependent). Butorphanol withdrawal was produced by terminating the infusion of butorphanol in dependent animals. Responses were studied 7 hr following termination (butorphanol withdrawal). IC(50) values from competition studies were estimated by fitting inhibition curves for both kappa(1)- and kappa(2)-opioid receptor assays. In both dependent and withdrawal groups, the IC(50) values obtained against [(3)H]CI-977 or [(3)H]bremazocine with nor-BNI were decreased (ratios of approximately 0.03-0.21 and approximately 0.05-0.42 vs. control, respectively) in brain regions, including frontal cortex, nucleus accumbens, claustrum, dorsal endopiriform nucleus, caudate putamen, parietal cortex, posterior basolateral amygdaloid nucleus, dorsomedial hypothalamus, hippocampus, posterior paraventricular thalamic nucleus, periaqueductal gray, substantia nigra, superficial gray layer of the superior colliculus, ventral tegmental area, and locus coeruleus, compared with control. These results indicate that, in butorphanol-dependent and butorphanol-withdrawal rats, the brain kappa(1)- and kappa(2)-opioid receptors developed a supersensitivity to antagonist binding.

Animals↗

PubMed2003

Regional specific increases of [3H]AMPA binding and mRNA expression of AMPA receptors in the brain of mu-opioid receptor knockout mice.

Previous pharmacological studies have indicated the possible existence of functional interactions between opioidergic and glutamatergic neurons in the CNS. In the present study, [(3)H]AMPA binding and the expression of mRNAs encoding flip and flop variants of three subtypes of AMPA glutamate receptor GluR1-3 were examined by in situ hybridization technique in order to investigate whether there is a change in the AMPA receptor system of mice lacking the mu-opioid receptor. In the mu-opioid receptor knockout mice, [(3)H]AMPA binding was increased in the hippocampal CA1 and dentate gyrus, cortex, and caudate putamen compared with that of the wild-type animals. The expression of GluR1 flip mRNA was increased in the cortex and caudate putamen of mu-opioid receptor knockout mice. The expression of GluR1 flop mRNA was increased in the cortex, caudate putamen, and hippocampal CA1 layer of mu-opioid receptor knockout mice. The expression of GluR2 flip mRNA was decreased in the hippocampal dentate gyrus of mu-opioid receptor knockout mice. The expression of GluR2 flop was not altered in any regions studied. The expression of GluR3 flip was increased in the cortical area and caudate putamen of mu-opioid receptor knockout mice. The expression of GluR3 flop was increased in the cortical area, hippocampal CA3 area, and caudate putamen of mu-opioid receptor knockout mice. These results indicate that [(3)H]AMPA binding and the expression of GluR1-3 mRNA were increased in a region and subunit specific manner, and suggest that changes in the AMPA receptor system are accompanied by the absence of mu-opioid receptor gene.

Animals↗

PubMed2002

Butorphanol dependence and withdrawal decrease hippocampal kappa 2-opioid receptor binding.

The present study examines the degree and distribution of alterations in the expression of kappa-opioid receptor subtypes using a model of chronic intracerebroventricular (i.c.v.) infusion of butorphanol. Autoradiographic characterization of binding for brain kappa(1) ([3H]CI-977)-, kappa(2) ([3H]bremazocine in the presence of DAMGO, DPDPE, and U-69,593)- and total kappa ([3H]bremazocine in the presence of only DAMGO and DPDPE)-opioid receptors was performed. Dependence was induced by a 72 h i.c.v. infusion with butorphanol (26 nmol/microl per hour) (butorphanol-dependent). Butorphanol withdrawal was produced by terminating the infusion of butorphanol in dependent animals. Responses were studied 7 h following termination (butorphanol-withdrawal). During both dependence and withdrawal phases, the binding signals for both kappa(1)- and kappa(2)-opioid receptors were significantly increased in certain regions, with especially marked increases in the frontal cortex, nucleus accumbens, parietal cortex, dorsomedial hypothalamus, ventral tegmental area and locus coeruleus. In contrast, a highly specific decrease in kappa(2)-, but increase in kappa(1)-, opioid receptor binding was noted in the hippocampus of rats in both butorphanol-dependent and-withdrawal groups. Therefore, alterations in kappa(1)- and kappa(2)-opioid receptors in the hippocampus may be differently involved in both adaptation to and recovery from chronic exposure to a mixed agonist/antagonist opioid analgesic. These results further illustrate the regional distribution of changes in binding characteristics of rat brain kappa(1)- and kappa(2)-opioid receptor subtypes in an established model of butorphanol dependence and withdrawal.

Animals↗

PubMed2002

Aroclor 1254-induced cytotoxicity in catecholaminergic CATH.a cells related to the inhibition of NO production.

The neuronal nitric oxide synthase (nNOS) specific inhibitor, 7-nitroindazole (7-NI), and the nitric oxide (NO) donor (S-nitroso-N-acetylpenicillarnine, SNAP) were used to study the role of NO in polychlorinated biphenyl (PCB: Aroclor 1254)-induced cytotoxicity in the immortalized dopaminergic cell line (CATH.a cells), derived from the central nervous system of mice. Treatment of the dopaminergic cells with various concentrations of Aroclor 1254 (0.5-10 microg/ml), a commercial PCB mixture, showed significant cytotoxicity as evaluated by lactate dehydrogenase (LDH) release and assessment of cell viability, depending on the concentration used. We also observed that Aroclor 1254 treatment reduced the level of nNOS expression. Furthermore, the cytotoxicity of Aroclor 1254 was augmented by 10 microM of 7-NI, which alone did not produce cytotoxicity, while it was protected by treatment with SNAP. Depending on the concentrations of Aroclor 1254 used, intracellular dopamine and dihydroxyphenylacetic acid (DOPAC) concentrations were significantly decreased. Therefore, these results suggest that PCBs have the potential for dopaminergic neurotoxicity, which may be related with the PCBs-mediated alteration of NO production originating from nNOS at least in part.

3,4-Dihydroxyphenylacetic Acid↗