• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.04a
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• pp.21-37
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• 2003

1. Stimulation of dopaminergic system by morphine was abolished in ${\mu}$-opioid receptor knockout mice. 2. Dopaminergic stimulation by opioid agonists, morphine, DPDPE, and U50488, acts independently. 3. Loss of ${\mu}$-opioid receptors is more sensitive to the response of NMDA-induced convulsion and increase in the expression of mRNA for NMDA receptors.

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2004.10a
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• pp.12-12
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• 2004

• Journal of Microbiology and Biotechnology
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• v.19 no.4
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• pp.424-430
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• 2009

IL-10 is an important anti-inflammatory cytokine that can inhibit the production of many pro-inflammatory cytokines. Both human and animal studies have shown that pro-inflammatory cytokines play an important role in pneumonia and other inflammatory lung diseases. In the present study, IL-10 knockout(KO) and wild-type mice were infected with Corynebacterium kutscheri to determine whether the severity of pathogenesis and whether protective immunity could be altered in the absence of IL-10. The survival rate was significantly lower in IL-10 KO mice than wild-type mice. The number of neutrophils in bronchoalveolar lavage fluid and blood were found to be higher in IL-10 KO mice than wild-type mice. IL-10 KO mice showed greater neutrophil infiltration, excessive inflammation, and weight-loss compared with wild-type mice. Furthermore, upregulation of IFN-$\gamma$ in bronchoalveolar lavage fluid, and upregulation of MIP-$1{\alpha}$ and IP-10 mRNA in the lungs of IL-10 KO mice compared with wild-type mice after C. kutscheri infection were observed. These results suggest that IL-10 plays an important role in the anti-inflammatory properties against C. kutscheri infection, and that lack of IL-10 leads to a more severe pulmonary inflammatory response. This increased susceptibility to C. kutscheri pneumonia is at least in part caused by IL-10 deficiency and severe recruitment of neutrophils.

• Molecules and Cells
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• v.45 no.12
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• pp.950-962
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• 2022

Aging is a major risk factor for common neurodegenerative diseases. Although multiple molecular, cellular, structural, and functional changes occur in the brain during aging, the involvement of caveolin-2 (Cav-2) in brain ageing remains unknown. We investigated Cav-2 expression in brains of aged mice and its effects on endothelial cells. The human umbilical vein endothelial cells (HUVECs) showed decreased THP-1 adhesion and infiltration when treated with Cav-2 siRNA compared to control siRNA. In contrast, Cav-2 overexpression increased THP-1 adhesion and infiltration in HUVECs. Increased expression of Cav-2 and iba-1 was observed in brains of old mice. Moreover, there were fewer iba-1-positive cells in the brains of aged Cav-2 knockout (KO) mice than of wild-type aged mice. The levels of several chemokines were higher in brains of aged wild-type mice than in young wild-type mice; moreover, chemokine levels were significantly lower in brains of young mice as well as aged Cav-2 KO mice than in their wild-type counterparts. Expression of PECAM1 and VE-cadherin proteins increased in brains of old wild-type mice but was barely detected in brains of young wild-type and Cav-2 KO mice. Collectively, our results suggest that Cav-2 expression increases in the endothelial cells of aged brain, and promotes leukocyte infiltration and age-associated neuroinflammation.

• Development and Reproduction
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• v.17 no.3
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• pp.179-186
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• 2013

Neural stem cells are found in adult mammalian brain regions including the subgranular zone (SGZ) of the dentate gyrus (DG) and the subventricular zone (SVZ). In addition to these two regions, other neurogenic regions are often reported in many species. Recently, the subcallosal zone (SCZ) has been identified as a novel neurogenic region where new neuroblasts are spontaneously generated and then, by Bax-dependent apoptosis, eliminated. However, the development of SCZ in the postnatal brain is not yet fully explored. The present study investigated the precise location and amount of neuroblasts in the developing brain. To estimate the importance of programmed cell death (PCD) for SCZ histogenesis, SCZ development in the Bax-knockout (KO) mouse was examined. Interestingly, an accumulation of extra neurons with synaptic fibers in the SCZ of Bax-KO mice was observed. Indeed, Bax-KO mice exhibited enhanced startle response to loud acoustic stimuli and reduced anxiety level. Considering the prevention of PCD in the SCZ leads to sensory-motor gating dysfunction in the Bax-KO mice, active elimination of SCZ neuroblasts may promote optimal brain function.

• Biomedical Science Letters
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• v.12 no.1
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• pp.53-56
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• 2006

The suprachiasmatic nucleus (SCN) of the anterior hypothalamus is the circadian pacemaker entrained to the 24-hr day by environmental time cues. Major circadian genes such as mPeriod ($mPer1{\sim}3$) and mCryptochrome ($mCry1{\sim}2$) are actively transcribed by the action of CLOCK/BMAL heterodimers, and in turn, these are being suppressed by the mPER/mCRY complex. In the study, the locomotor activity rhythms of mPer1 Knockout (KO) mice are measured, and the expression profiles of Heat Shock Protein 105kDa (HSP 105) genes in the SCN were measured by in situ hybridization. In agreement with previous reports, the locomotor activity rhythm of mPer1 KO mice was much shorter than that of wildtype. In addition, the total bout of activity of mPer1 KO was less in comparison to control mice. The expression of HSP 105 in the SCN of mPer1 KO mice was ranged from CT6 to CT22, with a peak level at CT14, implying that the gene are under the control of circadian clock. However, the expression of HSP 105 in the SCN of wildtype could not be detected in our study. Further analysis will reveal the direct or indirect regulation by mPer1 on the expression in the SCN and the role of the gene in the circadian clock.

• Toxicological Research
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• v.31 no.4
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• pp.347-354
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• 2015

Excess manganese (Mn) is neurotoxic. Increased manganese stores in the brain are associated with a number of behavioral problems, including motor dysfunction, memory loss and psychiatric disorders. We previously showed that the transport and neurotoxicity of manganese after intranasal instillation of the metal are altered in Hfe-deficient mice, a mouse model of the iron overload disorder hereditary hemochromatosis (HH). However, it is not fully understood whether loss of Hfe function modifies Mn neurotoxicity after ingestion. To investigate the role of Hfe in oral Mn toxicity, we exposed Hfe-knockout ($Hfe^{-/-}$) and their control wild-type ($Hfe^{+/+}$) mice to $MnCl_2$ in drinking water (5 mg/mL) for 5 weeks. Motor coordination and spatial memory capacity were determined by the rotarod test and the Barnes maze test, respectively. Brain and liver metal levels were analyzed by inductively coupled plasma mass spectrometry. Compared with the water-drinking group, mice drinking Mn significantly increased Mn concentrations in the liver and brain of both genotypes. Mn exposure decreased iron levels in the liver, but not in the brain. Neither Mn nor Hfe deficiency altered tissue concentrations of copper or zinc. The rotarod test showed that Mn exposure decreased motor skills in $Hfe^{+/+}$ mice, but not in $Hfe^{-/-}$ mice (p = 0.023). In the Barns maze test, latency to find the target hole was not altered in Mn-exposed $Hfe^{+/+}$ compared with water-drinking $Hfe^{+/+}$ mice. However, Mn-exposed $Hfe^{-/-}$ mice spent more time to find the target hole than Mn-drinking $Hfe^{+/+}$ mice (p = 0.028). These data indicate that loss of Hfe function impairs spatial memory upon Mn exposure in drinking water. Our results suggest that individuals with hemochromatosis could be more vulnerable to memory deficits induced by Mn ingestion from our environment. The pathophysiological role of HFE in manganese neurotoxicity should be carefully examined in patients with HFE-associated hemochromatosis and other iron overload disorders.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.3
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• pp.157-161
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• 2010

Heat shock proteins (HSPs) are specifically induced by various forms of stress. Hsp70.1, a member of the hsp70 family is known to play an important role in cytoprotection from stressful insults. However, the functional role of Hsp70 in motor function after spinal cord injury (SCI) is still unclear. To study the role of hsp70.1 in motor recovery following SCI, we assessed locomotor function in hsp70.1 knockout (KO) mice and their wild-type (WT) mice via the Basso, Beattie and Bresnahan (BBB) locomotor rating scale, before and after spinal hemisection at T13 level. We also examined lesion size in the spinal cord using Luxol fast blue/cresyl violet staining. One day after injury, KO and WT mice showed no significant difference in the motor function due to complete paralysis following spinal hemisection. However, when it compared to WT mice, KO mice had significantly delayed and decreased functional outcomes from 4 days up to 21 days after SCI. KO mice also showed significantly greater lesion size in the spinal cord than WT mice showed at 21 days after spinal hemisection. These results suggest that Hsp70 has a protective effect against traumatic SCI and the manipulation of the hsp70.1 gene may help improve the recovery of motor function, thereby enhancing neuroprotection after SCI.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1375-1383
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• 2015

Background: Objective Myocardin-related transcription factor (MRTF)-A is a Rho signaling-responsive co-activator of serum response factor (SRF). The purpose of this study is to investigate the role of MRTF-A and AQP1 (aquaporin 1) in pathological vascular remodeling. Materials and Methods: MRTF-A, AQP1 and neointima expression was detected both in the wire injured femoral arteries of wild-type mice and the atherosclerotic aortic tissues of $ApoE^{-/-}$ mice. Expression of ICAM-1, matrix metallopeptidase 9 (MMP-9) and integrin ${\beta}1$ were also assayed. The intercourse relationship between the molecules were investigated by interfering RNA and inhibitor assay. Results: MRTF-A and AQP1 expression were significantly higher in the wire injured femoral arteries of wild-type mice and in the atherosclerotic aortic tissues of $ApoE^{-/-}$ mice than in healthy control tissues. Both in wire-injured femoral arteries in MRTF-A knockout ($Mkl1^{-/-}$) mice and atherosclerotic lesions in $Mkl1^{-/-}$; $ApoE^{-/-}$ mice, neointima formation were significantly attenuated and the expression of AQP1 were significantly decreased. Expression of ICAM-1, matrix metallopeptidase 9 (MMP-9) and integrin ${\beta}1$, three SRF targets and key regulators of cell migration, and AQP1 in injured arteries was significantly weaker in $Mkl1^{-/-}$ mice than in wild-type mice. In cultured vascular smooth muscle cells (VSMCs), knocking down MRTF-A reduced expression of these genes and significantly impaired cell migration. Underlying the increased MRTF-A expression in dedifferentiated VSMCs were the down-regulation of microRNA-300. Moreover, the MRTF-A inhibitor CCG1423 significantly reduced neointima formation following wire injury in mice. Conclusions: MRTF-A could be a novel therapeutic target for the treatment of vascular diseases.

• Nutrition Research and Practice
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• v.18 no.2
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• pp.194-209
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• 2024

BACKGROUND/OBJECTIVES: High levels of plasma low-density lipoprotein (LDL) cholesterol are an important determinant of atherosclerotic lesion formation. The disruption of cholesterol efflux or reverse cholesterol transport (RCT) in peripheral tissues and macrophages may promote atherogenesis. The aim of the current study was to examine whether bioactive ellagic acid, a functional food component, improved RCT functionality and high-density lipoprotein (HDL) function in diet-induced atherogenesis of apolipoproteins E (apoE) knockout (KO) mice. MATERIALS/METHODS: Wild type mice and apoE KO mice were fed a high-cholesterol Paigen diet for 10 weeks to induce hypercholesterolemia and atherosclerosis, and concomitantly received 10 mg/kg ellagic acid via gavage. RESULTS: Supplying ellagic acid enhanced induction of apoE and ATP-binding cassette (ABC) transporter G1 in oxidized LDL-exposed macrophages, facilitating cholesterol efflux associated with RCT. Oral administration of ellagic acid to apoE KO mice fed on Paigen diet improved hypercholesterolemia with reduced atherogenic index. This compound enhanced the expression of ABC transporters in peritoneal macrophages isolated from apoE KO mice fed on Paigen diet, indicating increased cholesterol efflux. Plasma levels of cholesterol ester transport protein and phospholipid transport protein involved in RCT were elevated in mice lack of apoE gene, which was substantially reduced by supplementing ellagic acid to Paigen diet-fed mice. In addition, ellagic acid attenuated hepatic lipid accumulation in apoE KO mice, evidenced by staining of hematoxylin and eosin and oil red O. Furthermore, the supplementation of 10 mg/kg ellagic acid favorably influenced the transcriptional levels of hepatic LDL receptor and scavenger receptor-B1 in Paigen diet-fed apoE KO mice. CONCLUSION: Ellagic acid may be an athero-protective dietary compound encumbering diet-induced atherogenesis though improving the RCT functionality.