• Title/Summary/Keyword: Acetylcholine esterase

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Toxicoproteomic identification of $TiO_2$ nanoparticle-induced protein expression changes in mouse brain

  • Jeon, Yu-Mi;Park, Seul-Ki;Lee, Mi-Young
    • Animal cells and systems
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    • v.15 no.2
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    • pp.107-114
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    • 2011
  • A proteomic analysis of the proteins in mouse brain that were differentially expressed in response to $TiO_2$ nanoparticles was conducted to better understand the molecular mechanism of $TiO_2$ nanoparticle-induced brain toxicity at the protein level. A total of 990 proteins from mouse brain were resolved by two-dimensional gel electrophoresis. A comparative proteomic analysis revealed that the expression levels of 11 proteins were changed by more than 2-fold in response to $TiO_2$ nanoparticles: eight proteins were upregulated and three were downregulated by $TiO_2$ nanoparticles. In addition, the activities of several antioxidative enzymes and acetylcholine esterase were reduced in $TiO_2$ nanoparticle-exposed mouse brain. The protein profile alterations seem to be due to an indirect effect of $TiO_2$ nanoparticles, because $TiO_2$ nanoparticles were not detected in the brain in this investigation.

A Study on the Ultrastructural Changes of Cardiac Muscle in Dichlorvos Treated Albino Rat (Dichlorvos가 흰쥐 심근의 미세구조에 미치는 영향)

  • Baik, Tai-Kyoung;Lee, Wha-Mo;Chung, Ho-Sam
    • Applied Microscopy
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    • v.24 no.3
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    • pp.23-33
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    • 1994
  • It is well known that dichlorvos (DDVP), an organophosphate insecticide in common use, is so easily and rapidly hydrolyzed and excreted that it has usually little toxic effect on human body. In these days, however, it is widely used as an industrial and domestic insecticide and as an anthelmintic agent for animals, so that the accident of chemical poisoning occurs frequently. DDVP acts as a powerful inhibitor of carboxylic esterase, which can cause accumulation of acetylcholine at the synapses so paralysis of muscle and the transmission failure in cholinergic synapses dueing to desensitization of acetylcholin receptor may occure. Moreover accumulation of the acetylcholine brings about the elevation of the cyclic-AMP, which alters the cellular metabolisms of nucleic acid, carbohydrate, protein and lipid. Present study has undertaken to investigate the cardiotoxic effect of DDVP by electron microscopic study. A total of 30 Sprague-Dawley strain rats, weighing about 250gm were used as experimental animals. 2mg/kg/day of DDVP is intraperitonealy injected 3 times with intervals of every other day. On 1 day, 3 days, 5 days, 7 days and 14 days after drug administration, the animals were sacrified by cervical dislocation. Left ventricular cardiac muscles were resected and sliced into $1mm^3$. The specimens were embedded with Epon 812 and prepared by routine methods for electron microscopical observation. All preparations were stained with lead citrate and uranyl acetate and then observed with Hitachi-600 transmission electron microscope. The results were as follows: 1. In the cardiac muscle of DDVP treated rats, mitochondria with disorganized double membrane and mitochondrial crista, and vacuole formation in mitochondrial matrix were observed. But structures of mitochondria were recovered to normal in 14 days group. 2. In the cardiac muscle of DDVP treated rats, cisternae of sarcoplasmic reticulum were dilated and sacculated. But these changes were recovered to normal in 14 days group. 3. In the cardiac muscle of DDVP treated rats, glycogen particles around damaged myofibrils were decreased. But amount of glycogen particles were restored in 14 days group. 4. In the cardiac muscle of DDVP treated rats, disruption and discontinuation of myofilaments and disorganization of Z-disc were observed. But the structures of myofibrils were recovered to normal in 14 days group. It is consequently suggested that DDVP would induce the reversible degenerative changes on the ultrastructures in cardiac muscle of rat.

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Perilla Frutescens Extract Protects against Scopolamine-Induced Memory Deficits in Mice (스코폴라민으로 유도한 기억력 손상 모델에서 소엽 추출물의 보호 효과)

  • Lee, Jihye;Lee, Eunhong;Jung, Eun Mi;Kim, Dong Hyun;Kim, Sung-kyu;Park, Mi Hee;Jung, Ji Wook
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.35 no.3
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    • pp.97-103
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    • 2021
  • Perilla frutescens (P. frutescens) is an important herb used for many purposes such as medicinal, aromatic, and functional food in Asian countries and has beneficial effects such as antioxidant activity, anti-inflammation activity, anti-depression activity, and anxiolytic activity. However, there have been no studies on the protective effect of P. frutescens extract (PFE) on amnesia in vivo. The present study aimed to investigate whether PFE protects memory deficit using a scopolamine-induced mice model and elucidate the underlying mechanisms involved. The protective effect of PFE against scopolamine-induced memory deficits was investigated using Y-maze, passive avoidance, and Morris water maze tests. Furthermore, the potential mechanisms of PFE in improving memory capabilities related to the cholinergic system and antioxidant activity were examined. PFE significantly increased spontaneous alternation in the Y-maze test, step-through latency in the passive avoidance test, and swimming time in the target quadrant in the probe test when compared to the scopolamine-treated group. Likewise, PFE significantly decreased escapes latency in the Morris water maze test. PFE could not regulate cholinergic function in acetylcholine level and acetylcholine esterase activity. However, PFE increased DPPH radical scavenging activity dose-dependently and total polyphenol content was 127.7±1.2 ㎍ GAE/mg. The results showed that the PFE could be a preventive and/or therapeutic candidate for memory and cognitive dysfunction in Alzheimer's disease.

Cognitive-enhancing Effects of a Fermented Milk Product, LHFM on Scopolamine-induced Amnesia (발효유 산물인 LHFM의 인지기능 개선 효과)

  • Jeon, Yong-Jin;Kim, Jun-Hyeong;Lee, Myong-Jae;Jeon, Woo-Jin;Lee, Seung-Hun;Yeon, Seung-Woo;Kang, Jae-Hoon
    • Korean Journal of Food Science and Technology
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    • v.44 no.4
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    • pp.428-433
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    • 2012
  • Probiotics and their products, such as yogurt and cheese have been widely consumed in many countries with proven health benefits including anti-microbial activity and anti-diarrheal activity. LHFM (Lactobacillus helveticus - fermented milk) is a processed skim milk powder, fermented by a probiotics, L. helveticus IDCC3801. In the present study, we aimed to investigate the neuroprotective effects and the cognitive improvements of LHFM. LHFM itself did not show any cytotoxicity to the human neuroblastoma cell line, SH-SY5Y; however, it dose-dependently protected against glutamate-induced neuronal cell death. LHFM also attenuated scopolamine-induced memory deficit in Y-maze and Morris-water maze. In the analysis of hippocampus after a behavior test, LHFM significantly increased the acetylcholine level and also inhibited acetylcholine esterase activity. Therefore, the raised acetylcholine release partially contributes to the improvement of learning and memory by a treatment with LHFM. These results suggest that LHFM is an effective material for prevention or improvement of cognitive impairments caused by neuronal cell damage and central cholinergic dysfunction.

Effect of Gagamjeongji-hwan and Evodiae Fructus on Memory Impairment and Neuronal Damage Induced by Focal Ischemia in the Rat (국소 전뇌 허혈 모델 백서에서 가감정지환(加減定志丸)과 오수유(吳茱萸)가 기억증진과 신경세포보호에 미치는 효과)

  • Kim, Hoi-Young;Son, Hyun-Soo;Kang, Ji-Hong;Choi, U-Jeong;Lee, Jin-Seok;Yang, Jae-Hoon;Seol, Jae-Kyun;Lee, Eon-Jeong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.6
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    • pp.1487-1494
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    • 2008
  • This study was conducted to determine the effect of Gagamjeongji-hwan (JJH)(Jiajiandingzhi-wan) and Evoidae Fructus (EF) on learning and memory disturbance and neuronal damage induced by focal ischemia in the rat. Rats were used for testing in the following three. Morris Water Maze, Cholineacetyltransferase (ChAT) immunohistochemistry, acetylcholine esterase (AchE) histochemistry. JJH+ISCH group (ischemia-induced rats pretreated with JJH) and EF+ISCH group (ischemia-induced rats pretreated with EF) significantly reduced the latency of swimming time, compared with those of ISCH group (ischemia-induced rats) in morris water maze acquisition test. JJH+ISCH group attenuated ischemia.induced learning and memory damage in morris water maze retention test. The density of ChAT neurons of the JJH+ISCH and EF+ISCH group in the hippocampal CA1 area was increased, compared to that of SAL+ISCH group (ischemia-induced rats pretreated with SAL). The density of AchE neurons of the JJH+ISCH and EF+ISCH group in the hippocampal CA1 and CA3 area was increased, compared to that of SAL+ISCH group. These results suggest that Gagamjeongji-hwan (JJH) and Evodiae Fructus (EF) may have significant protective effects on ischemia-induced brain damage and memory impairments.

The Effects of Acupuncture at Sobu (HT8) and Haenggan (LR2) on Scopolamine-induced Cognitive Impairment in Rat Model

  • Song, Ho-Joon;Cho, Myoung-Rae
    • Journal of Acupuncture Research
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    • v.35 no.1
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    • pp.28-36
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    • 2018
  • Background: This study investigated the effects of acupuncture at Sobu (HT8) and Haenggan (LR2) on scopolamine-induced, cognitively impaired rats. Methods: Scopolamine-treated Sprague-Dawley rats were divided into 6 groups; normal, control, HT8, LR2, HT8 + LR2 and sham group. Cognitive impairment was induced by scopolamine, in control, and then in HT8, LR2, HT8 + LR2 and sham groups. Acupuncture treatment was performed at HT8, LR2, HT8 + LR2, and a random acupoint, respectively, every other day for 2 weeks. After each treatment, behavior change was observed and the rats were sacrificed. The change in brain-derived neurotrophic factor, glutathione peroxidase, and superoxide dismutase activity was evaluated by polymerase chain reaction. Results: Latency time to target in Morris Water-Maze test for the HT8 + LR2 group showed a significant decrease compared with control (p<0.05). Target crossing times and time zone ratios in Morris Water-Maze test for HT8 + LR2 group showed a significant increase compared with control (p<0.01). In the Y-Maze test the HT8 + LR2 group showed a significant increase compared with control (p<0.05). Brain-derived neurotrophic factor, glutathione peroxidase, and superoxide dismutase, in the HT8 + LR2 group, showed a significantly increased level compared with control (p<0.05). Neural activity of acetylcholine esterase in HT8 + LR2 group showed a significant decrease compared with the control group (p<0.01), choline acetyltransferase activity in the HT8 + LR2 group showed a significant increase compared with control (p<0.05). Conclusion: Acupuncture at HT8 + LR2 restored scopolamine-induced cognitive impairment, suggesting acupuncture could be an alternative to improve cognitive function.

Effects of Korean Mountain Ginseng Leaves and Its Active Constituents on Scopolamine-induced Amnesia in Mouse (장뇌삼 잎 추출물의 분획물이 Scopolamine으로 유도된 Mouse의 기억력 개선에 미치는 영향)

  • Kim, Ju-Bong;Kim, Soo-Hyun;Park, Sun-Young;Chung, Dae-Kyoo
    • Journal of Oriental Neuropsychiatry
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    • v.21 no.1
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    • pp.125-144
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    • 2010
  • Objectives: The purpose of this study was to characterize the effect of the fraction of Korean mountain ginseng folium (FKG) on the learning and memory impairments induced by scopolamine. Methods: The memory ameliorating effect of FKG was investigated using a passive avoidance test, the Y-maze test, and the Morris water maze test in mice. Drug-induced amnesia was induced by treating animals with scopolamine(1mg/kg, i.p.). Results: FKG (2 or 4mg/kg, p.o.) administration significantly reversed scopolamine-induced cognitive impairments in mice by the passive avoidance test and the Y-maze test(P<0.05), and also improved escape latency in the Morris water maze test at 2 or 4mg/kg(P<0.05). Although FKG has little inhibitory activity for AChE (IC50 value; 1847 ${\mu}g/ml$) in an invitro study, phosphorylated extracellular signal-regulated kinase(pERK) was increased by the administration of FKG inhippocampus on immunohistochemistry. Conclusions: These results suggest that FKG may be a useful cognitive impairment treatment, and its beneficial effects are mediated, in part, via activation of ERK pathway.

Effect of the Electroacupuncture at ST36 in TMT-induced Memory Deficit Rats

  • Shim, Hyun-Soo;Park, Hyun-Jung;Lee, Hye-Jung;Shim, In-Sop
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.4
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    • pp.691-696
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    • 2011
  • In order to the neuroprotective effect of electroacupuncture (EA), the present study examined the effects of electroacupuncture inacupoint ST36 (Stomach 36) on trimethyltin chloride (TMT)-induced cognitive impairments rat using the Morris water maze (MWM) task and immunohistochemistry staining. The rats were randomly divided into the following groups: naive rat (Normal), TMT injection rat (Control), TMT injection + EA treated rat inacupoint ST36 (ST36) and TMT injection + EA treated rat in non-acupoint, base of tail (Non-AC). Electroacupuncture (2Hz, 2mA, and 10 minutes)was applied either to the acupuncture point ST36 or the nonacupuncture point in the tail for the last 14 days. In the water maze test, the animals were trained to find a platform in a fixed position during 4d and then received 60s probe trial on the $5^{th}$ day following removal of platform from the pool. Rats with TMT injection showed impaired learning and memory of the tasks and treatment with EA in acupoint ST36 (P<0.05) produced a significant improvement in escape latency to find the platform after $2^{nd}$ day and retention trial in the Morris water maze. Consistent with behavioral data, treatment with EA in acupoint ST36 also significantly increased expression of Choline acetyltransferase (ChAT) and Acetylcholinesterase (AChE) immunoreactive neurons in the hippocampus compared to the Control group. These results demonstrated that EA in acupoint ST36 has a protective effect against TMT-induced neuronal and cognitive impairments. The present study suggests that EA in acupoint ST36 might be useful in the treatment of TMT-induced learning and memory deficit.

Anti-oxidative and Neuroprotective Activities of Pig Skin Gelatin Hydrolysates (돈피젤라틴 효소분해물의 항산화 활성 및 신경세포보호효과)

  • Kim, Dong Wook;Park, Kimoon;Ha, Goeun;Jung, Ju Ri;Chang, Ounki;Ham, Jun-Sang;Jeong, Seok-Geun;Park, Beom-Young;Song, Jin;Jang, Aera
    • Food Science of Animal Resources
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    • v.33 no.2
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    • pp.258-267
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    • 2013
  • This study was conducted to determine the antioxidative and neuroprotective effect of pig skin extracts (PS) and pig skin gelatin hydrolysates (LPS) using a human neuroblastoma cell line (SH-SY5Y). The extraction yield of PS was 3 fold higher than that of LPS. The protein content of PS was about 10 fold higher than that of LPS (p<0.05). Also LPS increased antioxidative activity dose dependently, and the activity was significantly higher than PS at all concentration (p<0.05). DPPH radical scavenging activity of LPS at 50 mg/mL was 92.97%, which was similar to $1{\mu}M$ vitamin C as a positive control. ABTS radical scavenging activity of LPS (20 mg/mL) was 89.83% and oxygen radical absorbance capacity of LPS at 1 mg/mL was $141.39{\mu}M$ Trolox Equvalent/g. No significant change of human neuroblastoma cells was determined by MTT test. Cell death by oxidative stress induced by $H_2O_2$ and amyloid beta 1-42 ($A{\beta}_{1-42}$) was protected by LPS rather than PS. Acetylcholine esterase was significantly inhibited, by up to 33.62% by LPS at 10 mg/mL. Therefore, these results suggest that pig skin gelatin hydrolysates below 3 kDa have potential to be used as anti-oxidative and neuroprotective functional additives in the food industry, while further animal test should be determined in the future.

Effect of Daebo (Castanea crenata) Inner Skin Extract on TMT-induced Learning and Memory Injury (TMT 유도성 인지 기능 상실에 대한 대보(밤 품종) 내피 추출물의 효과)

  • Kim, Hyeon-Ju;Jeong, Ji Hee;Jo, Yu Na;Jin, Dong Eun;Jin, Su Il;Kim, Man-Jo;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.45 no.5
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    • pp.661-665
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    • 2013
  • The aim of this study was to investigate the anti-amnesic effect of daebo (Castanea crenata) extract on trimethyltin chloride (TMT)-induced learning and memory impairment, in vivo. The inner skin of daebo was extracted using distilled water under reflux conditions. At the end of the adaptation period, ICR mice were divided into a control group, a TMT injection group (negative control), and a sample group (C5: 5 mg/kg body weight; C10: 10 mg/kg body weight; and C20: 20 mg/kg body weight), and were tested with learning and memory tests. The ethylacetate fraction of the daebo inner skin extract was found to increase TMT-induced memory deficit in the Y-maze and passive avoidance test. Brain tissue analysis showed that the ethylacetate fraction of daebo extract lowered the acetylcholine esterase (AChE) activity and malondialdehyde (MDA) content of neuronal cells, both of which are indicative of lipid peroxidation.