Dose-response and relative biological effectiveness of fast neutrons: Induction of apoptosis and inhibition of neurogenesis in the hippocampus of adult mice.

Yang, Miyoung,Kim, Joong-Sun,Song, Myoung-Sub,Kim, Jong-Choon,Shin, Taekyun,Lee, Seung-Sook,Kim, Sung-Ho,Moon, Changjong Taylor Francis 2010 International Journal of Radiation Biology Vol.86 No.6

<P>Purpose: Our study compared the effects of high linear energy transfer (LET) fast neutrons on the induction of apoptosis and reduction of neurogenesis in the hippocampus of adult ICR mice with those of low-LET (60)Co gamma-rays, to evaluate the relative biological effectiveness (RBE) of fast neutrons in the adult hippocampal dentate gyrus (DG). Materials and Methods: The mice were exposed to 35 MeV fast neutrons or (60)Co gamma-rays. We evaluated acutely the incidence of apoptosis and expression of Ki-67 (a protein marker for cell proliferation originally defined by the monoclonal antibody Kiel-67) and doublecortin (DCX: an immature progenitor neuron marker) in the hippocampus after a single whole-body irradiation. Results: The number of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labelling (TUNEL)-positive apoptotic nuclei in the DG increased and both Ki-67- and DCX-positive cells declined in a dose-dependent pattern, with fast neutrons or gamma-rays. In the hippocampus, which showed an apoptosis frequency between 2 and 8 per DG, the RBE of fast neutrons was approximately 1.9. Additionally, the inhibitory effects of fast neutrons on the expression frequencies of Ki-67 (4-8) and DCX (8-32) were approximately 3.2 and 2.5 times, respectively, the effects of gamma-rays at the same dose. Conclusions: Increased apoptotic cell death and decreased neurogenesis in the hippocampal DG were seen in a dose-dependent pattern after exposure to fast neutrons and gamma-rays. In addition, the different rate of hippocampal neurogenesis between different radiation qualities may be an index of RBE.</P>

Evaluation of effect of red ginseng on ovariectomy-induced bone loss in C3H/HeN mice

Miyoung Yang, Hyosun Jang, Hae-June Lee, Changjong Moon, Jong-Choon Kim, Jong-Sik Jang, Uhee Jung, Sung-Kee Jo, Sung-Ho Kim 충북대학교 동물의학연구소 2014 Journal of Biomedical and Translational Research Vol.15 No.1

Panax ginseng, also known as Korean ginseng, has long been used as a broad tonic in Oriental medicine to augment vitality, health, and longevity, particularly in older people. This study investigated the effects of Korean red ginseng (RG) on bone loss in ovariectomized (OVX) mice. C3H/HeN mice (10-weeks-old) were divided into sham and OVX groups. OVX mice were treated with vehicle, 17β-estradiol (E2), RG (oral administration, 250 mg/kg/day), or RG (intraperitoneal administration, 50 mg/kg/every other day) for 6 weeks. Serum E2 concentration and alkaline phosphatase (ALP) activity were measured. Tibiae were analyzed using microcomputed tomography. Biomechanical properties and osteoclast surface level were measured. There was no significant difference in the degree of grip strength, body weight, uterine weight, mechanical property, tibiae length, or tibiae weight between the OVX and RG-treated groups. Compared with the OVX group, the serum ALP level was significantly lower in the RG-treated groups. Serum E2 levels and osteoclast surface levels did not change between the OVX and RG-treated groups. RG could not preserve trabecular bone volume, trabecular bone number, trabecular separation, trabecular thickness, structure model index, or bone mineral density of the proximal tibiae metaphysic. In conclusion, there was no definite effect of RG on OVX-induced bone loss in C3H/HeN mice.

Neurotoxicity of cancer chemotherapy

Yang, Miyoung,Moon, Changjong Medknow PublicationsMedia Pvt Ltd 2013 Neural regeneration research Vol.8 No.17

<P>There is accumulating clinical evidence that chemotherapeutic agents induce neurological side effects, including memory deficits and mood disorders, in cancer patients who have undergone chemotherapeutic treatments. This review focuses on chemotherapy-induced neurodegeneration and hippocampal dysfunctions and related mechanisms as measured by <I>in vivo</I> and <I>in vitro</I> approaches. These investigations are helpful in determining how best to further explore the causal mechanisms of chemotherapy-induced neurological side effects and in providing direction for the future development of novel optimized chemotherapeutic agents.</P>

A 3–10 GHz CMOS low-noise amplifier using wire bond inductors

Yang, Miyoung,Ha, Mincheol,Park, Youngjin,Eo, Yunseong Wiley Subscription Services, Inc., A Wiley Company 2009 MICROWAVE AND OPTICAL TECHNOLOGY LETTERS Vol.51 No.2

<P>In this article, a small-sized 3–10 GHz CMOS LNA for ultra-wideband (UWB) applications is presented. To reduce 2 on-chip inductors, wire bond inductors are used instead of input inductor of multisectional reactive network and source degeneration inductor. The noise figure of low-noise amplifier (LNA) is 4 dB at minimum and IIP3 + 1.1 dBm at 5 GHz, respectively. The current consumption is 4 mA at 1.8 V supply. The LNA chip size including pads is 1 mm × 1 mm. © 2008 Wiley Periodicals, Inc. Microwave Opt Technol Lett 51: 414–416, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.24082</P>

Cytotoxicity of gamma-ray on immature hippocampal cultured cells

Miyoung Yang,Hyosun Jang,Juhwan Kim,Joong-Sun Kim,Sung-Ho Kim,Jong-Choon Kim,Taekyun Shin,Changjong Moon 한국실험동물학회 2010 한국실험동물학회 학술발표대회 논문집 Vol.2010 No.8

Temporal profiles of synaptic plasticity-related signals in adult mouse hippocampus with methotrexate treatment

Yang, Miyoung,Kim, Juhwan,Kim, Sung-Ho,Kim, Joong-Sun,Shin, Taekyun,Moon, Changjong Medknow PublicationsMedia Pvt Ltd 2012 Neural regeneration research Vol.7 No.21

<P>Methotrexate, which is used to treat many malignancies and autoimmune diseases, affects brain functions including hippocampal-dependent memory function. However, the precise mechanisms underlying methotrexate-induced hippocampal dysfunction are poorly understood. To evaluate temporal changes in synaptic plasticity-related signals, the expression and activity of N-methyl-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, extracellular signal-regulated kinase 1/2, cAMP responsive element-binding protein, glutamate receptor 1, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor were examined in the hippocampi of adult C57BL/6 mice after methotrexate (40 mg/kg) intraperitoneal injection. Western blot analysis showed biphasic changes in synaptic plasticity-related signals in adult hippocampi following methotrexate treatment. N-methyl-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, and glutamate receptor 1 were acutely activated during the early phase (1 day post-injection), while extracellular signal-regulated kinase 1/2 and cAMP responsive element-binding protein activation showed biphasic increases during the early (1 day post-injection) and late phases (7–14 days post-injection). Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression increased significantly during the late phase (7–14 days post-injection). Therefore, methotrexate treatment affects synaptic plasticity-related signals in the adult mouse hippocampus, suggesting that changes in synaptic plasticity-related signals may be associated with neuronal survival and plasticity-related cellular remodeling.</P>

Acute treatment with methotrexate induces hippocampal dysfunction in a mouse model of breast cancer

Yang, Miyoung,Kim, Joong-Sun,Kim, Juhwan,Jang, Sungwoong,Kim, Sung-Ho,Kim, Jong-Choon,Shin, Taekyun,Wang, Hongbing,Moon, Changjong Elsevier 2012 Brain research bulletin Vol.89 No.1

<P>Methotrexate (MTX) is a well-known cytostatic agent used in adjuvant chemotherapy for breast cancer, that has neurological side effects, including depression and cognitive impairment. We investigated the neurotoxic effects of MTX on the hippocampus and hippocampus-dependent behaviors in breast cancer cell line (FM3A)-inoculated tumor-bearing mice. In addition, we evaluated the changes in inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in the hippocampus of tumor-bearing mice after treatment with MTX. Depressive-like behavior test (tail-suspension test, TST) and learning and memory tasks (passive avoidance) were administered 24h after MTX (40 mg/kg, i.p.) injection. MTX-treated tumor-bearing mice showed significant depressive-like behaviors and cognitive impairment. Treatment with MTX significantly decreased the number of doublecortin (a marker for immature progenitor neurons)-positive cells in the hippocampal dentate gyrus of tumor-free and tumor-bearing mice. Moreover, treatment with MTX significantly upregulated proinflammatory enzymes, including iNOS and COX-2, in tumor-bearing mice. These findings indicate that the acute neurotoxic effect of MTX leads to hippocampal dysfunction including depressive-like behaviors and memory deficits, which may be related to an inhibition of neurogenesis and an increase of the inflammatory response in the hippocampus of a mouse model of breast cancer.</P>

Fast neutron irradiation deteriorates hippocampus-related memory ability in adult mice

Yang, Miyoung,Kim, Hwanseong,Kim, Juhwan,Kim, Sung-Ho,Kim, Jong-Choon,Bae, Chun-Sik,Kim, Joong-Sun,Shin, Taekyun,Moon, Changjong The Korean Society of Veterinary Science 2012 JOURNAL OF VETERINARY SCIENCE Vol.13 No.1

<P>Object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice exposed to cranial fast neutron irradiation (0.8 Gy) were examined to evaluate hippocampus-related behavioral dysfunction following acute exposure to relatively low doses of fast neutrons. In addition, hippocampal neurogenesis changes in adult murine brain after cranial irradiation were analyzed using the neurogenesis immunohistochemical markers Ki-67 and doublecortin (DCX). In the object recognition memory test and contextual fear conditioning, mice trained 1 and 7 days after irradiation displayed significant memory deficits compared to the sham-irradiated controls. The number of Ki-67- and DCX-positive cells decreased significantly 24 h post-irradiation. These results indicate that acute exposure of the adult mouse brain to a relatively low dose of fast neutrons interrupts hippocampal functions, including learning and memory, possibly by inhibiting neurogenesis.</P>

Toluene Induces Depression-Like Behaviors in Adult Mice

Miyoung Yang,Sung-Ho Kim,Jong-Choon Kim,Taekyun Shin,Changjong Moon 한국독성학회 2010 Toxicological Research Vol.26 No.4

It has been clinically reported that toluene causes mental depression in humans. However, the detrimental effects of toluene exposure on brain function and the relation between features of mental depression and toluene exposure are poorly understood. This study evaluated depression-like behaviors in adult C57BL/6 mice after administration of toluene, and elucidated the effects of classical antidepressants on the depression-like behaviors. For the estimation of depression-like behaviors, tail suspension test (TST) and forced-swim test (FST) were performed 1, 4 and 16 days after toluene (0~1000 ㎎/㎏ bw) treatment. In addition, classical antidepressants such as fluoxetine (FLX, 20 ㎎/㎏ bw) and imipramine (IMI, 40 ㎎/㎏ bw) were administered 12 h and 1 h before the tests. In the TST and FST, toluene-treated mice exhibited a longer duration of immobility than vehicle-treated mice 1 and 4 days after toluene treatment. The depression-like behaviors were significantly reversed by FLX and IMI. The weight of the adrenal gland and the size of adrenocortical cells were significantly higher in toluene-treated mice compared to vehicle-treated controls. It is suggested that acute toluene exposure of adult mice is sufficiently detrimental to induce depression. In addition, this study has established a mouse model for a depressive state induced by toluene treatment.

Evaluation of biological responses in rats experimentally exposed to crude oil

Sung-Ho Kim, Miyoung Yang, Changjong Moon, Jong-Choon Kim, Chun-Sik Bae, Jong-Sik Jang, Young-Hyun Choi, Su-Ryeon Noh 충북대학교 동물의학연구소 2012 Journal of Biomedical and Translational Research Vol.13 No.4

To evaluate the acute to chronic effects of crude oil exposure on hematological and blood biochemical toxicities, Sprague-Dawley rats were given oral doses of 0, 50, or 100 mg/kg BW/day of Iranian heavy crude oil for a period of four weeks. In the acute phase of exposure (one day after four weeks of oil treatment), decreases in weight of thymus, serum level of interferon gamma (IFN-γ), superoxide dismutase (SOD), and catalase activities in liver or kidney, and increase in weight of adrenal gland occurred after oral administration of crude oil. In body weight, histopathological examination, hematological and blood biochemical analyses in the acute phase of exposure, no significant differences were observed among the experimental groups. In the subchronic and chronic phase of exposure (two months and six months after four weeks of oil treatment), the changes of biomarkers were normalized, except the indicators of oxidative stress. Our findings showed that the bioassay on the indicators of oxidative stress is a sensitive method for determining exposure to crude oil in rats.