• 대한수의학회지
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• 제51권3호
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• pp.185-191
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• 2011

Trimethyltin chloride (TMT) has been used as a neurotoxin for inducing brain dysfunction and neuronal death. Neuronal death in the hippocampus by TMT may generate excessive nitric oxide, but there are few studies about nitric oxide synthase enzyme involved in the synthesis of nitric oxide. The purpose of present study is to analyze the TMT toxicity in each region of rat hippocampus. To evaluate the involvement of nitric oxide, we analyzed the effects of aminoguanidine known as a selective inhibitor for inducible nitric oxide synthase on behavioral changes and the hippocampus of rat by TMT toxicity. 6-week-old male Sprague-Dawley rats were administered with a single dose of TMT (8 mg/kg b.w., i.p.) and the control group was similarly administered with distilled water. TMT + aminoguanidine-treated groups were administered with aminoguanidine (10 mg/kg or 100 mg/kg b.w., i.p.) for 3 days prior to TMT injection. The rats were sacrificed 2 days after TMT administration. In the TMT-treated group, a number of cell losses were seen in CA1, CA3 and the dentate gyrus. In the TMT + aminoguanidine-treated group, neuronal death was seen in CA1 and CA3, but reduced in the dentate gyrus compared to the TMT-treated group. Western blot analysis showed that cleaved caspase-3 expression was increased in the TMT-treated group compared to the control group. However, the expression significantly declined in the TMT + aminoguanidine-treated group. The present findings suggest that inducible nitric oxide synthase is involved in neuronal death induced by TMT.

• Biomolecules & Therapeutics
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• 제24권3호
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• pp.328-337
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• 2016

We examined whether wogonin (WO) improved hippocampal neuronal activity, behavioral alterations and cognitive impairment, in rats induced by administration of trimethyltin (TMT), an organotin compound that is neurotoxic to these animals. The ability of WO to improve cognitive efficacy in the TMT-induced neurodegenerative rats was investigated using a passive avoidance test, and the Morris water maze test, and using immunohistochemistry to detect components of the acetylcholinergic system, brain-derived neurotrophic factor (BDNF), and cAMP-response element-binding protein (CREB) expression. Rats injected with TMT showed impairments in learning and memory and daily administration of WO improved memory function, and reduced aggressive behavior. Administration of WO significantly alleviated the TMT-induced loss of cholinergic immunoreactivity and restored the hippocampal expression levels of BDNF and CREB proteins and their encoding mRNAs to normal levels. These findings suggest that WO might be useful as a new therapy for treatment of various neurodegenerative diseases.

• Toxicological Research
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• 제6권2호
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• pp.191-204
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• 1990

Trimethyltin (TMT) induced lesions in the rat hippocampal formation was reviewed. Adult rats were treated with a single dose of 6.0 mg TMT/kg b.w. and were sacrificed between 3-60 days following exposure. On the hippocampal formation, the granule cells of fascia dentata showed early changes which subsided considerably at a later time when the destruction of the pyramidal neurons of the Ammon's horn became increasingly pronounced with time, leading to severe destruction of the structure. It is interesting to note that there was an inverse relationship of pathological involvement between the f.d. granule cells and the Ammon's horn neurons; i.e., when there was a large sparing of the granule cells. there was an extensive damage to the Ammon's horn and vice versa. This inverse relationship was also true between the $CA_3$neurons and the $CA_{1,2}$neurons in the Ammon's horn. Progressive zinc loss, as demonstrated by Timm's method, on the Mossy fibers was also observed. Similar Mossy fiber zinc depletion has been demonstrated in electrical stimulatory excitation condition of the perforant path to the hippocampus. Depletion of corticosterone, an inhibitor to the hippocampal neurons, by means of adrenalectomy will exaggerate the TMT induced hippocampal lesion. Neonatal study revealed that a unique degenerative pattern of the Ammon's horn could be established in accordance with exposure to TMT at specific maturation periods of the fippocampal formation: increasing destruction of the Ammon's horn with increasing synaptogenesis between the f.d. granule cells and the Ammon's horn neurons. Thus it is apparent that the damage of the Ammon's horn, upon exposure to TMT, may depend on the integrity and functional state of the f.d. granule cells. A hyperexcitory scheme and mechanism as the toxicity basis of TMT in the hippocampal formation is proposed and discussed.

• 동의생리병리학회지
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• 제25권4호
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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.

• 한국약용작물학회지
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• 제19권6호
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• pp.456-463
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• 2011

The present study examined the effects of Korean white ginseng (WG, Panax ginseng C. A. Meyer) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The rats were administered with saline or WG (WG 100 or 300 mg/kg, p.o.) daily for 21 days. The cognitive improving efficacy of WG on the amnesic rats, which was induced by TMT, was investigated by assessing the Morris water maze test and by performing immunohistochemistries on choline acetyltransferase (ChAT), acetylcholinesterase (AchE), cAMP responsive element binding protein (CREB) and brain derived neurotrophic factor (BDNF). The rats treated with TMT injection (control group) showed impaired learning and memory of the tasks, but the rats treated with TMT injection and WG administration produced significant improvement of the escape latency to find the platform in the Morris water maze at the 2nd and 4th days compared to that of the control group. In the retention test, the WG 100 and WG 300 groups showed significantly increased crossing number around the platform compared to that of the control group (p < 0.001). Consistently with the behavioral data, result of immunohistochemistry analysis showed that WG 100 mg/kg significantly alleviated the loss of BDNF-ir neurons in the hippocampus compared to that of the control group (p < 0.01). Also, treatment with WG has a trend to be increased the cholinergic neurons in the hippocampal CA1 and CA3 areas as compared to that of the control group. These results suggest that WG may be useful for improving the cognitive function via regulation of neurotrophic activity.

• 대한약침학회지
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• 제20권1호
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• pp.10-17
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• 2017

Objectives: Boswellic acid (BA), a compound isolated from the gum-resin of Boswellia carterii, is a pentacyclic terpenoid that is active against many inflammatory diseases, including cancer, arthritis, chronic colitis, ulcerative colitis, Crohn's disease, and memory impairment, but the mechanism is poorly understood. This study investigated the effects of boswellic acid on spatial learning and memory impairment induced by trimethyltin (TMT) in Wistar rats. Methods: Forty male Wistar rats were randomly divided into 5 groups: Normal group, TMT-administrated rats (8.0 mg/kg, Intraperitoneally, i.p.) and TMT + BA (40, 80 and 160 mg/kg, i.p.)-administrated rats. BA was used daily for 21 days. To evaluate the cognitive improving of BA, we performed the Morris water maze test. Moreover, to investigate the neuroprotective effect of BA, we determined the acetylcholinesterase (AchE) activity, the malondialdehyde (MDA) level as a marker of lipid peroxidation, and the glutathione (GSH) content in the cerebral cortex. Results: Treatment with TMT impaired learning and memory, and treatment with BA at a dose of 160 mg/kg produced a significant improvement in learning and memory abilities in the water maze tasks. Consistent with behavioral data, the activity of AChE was significantly increased in the TMT-injected rats compared to the control group (P < 0.01) whereas all groups treated with BA presented a more significant inhibitory effect against AChE than the TMT-injected animals. In addition, TMT reduced the GSH content and increased the MDA level in the cerebral cortex as compared to the control group) P < 0.01). On the other hand, treatment with BA at 160 mg/kg slightly increased the GSH content and reduced the MDA level in comparison to the TMT-administered group (P < 0.01). Conclusion: The above results suggest that the effect of BA in improving the cognitive function may be mediated through its antioxidant activity.

• 환경생물
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• 제21권2호
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• pp.164-169
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• 2003

유기주석화합물은 농업과 산업분야에서 많이 쓰이고, 이들은 수계환경으로 유입되어 물이나 저질 중의 세균들에 의해 분해되어 최종적으로는 무기주석으로 된다. Trialkyltin 화합물이 해양생물에 미치는 영향에 관해서는 많은 연구가 있지만, 해양생태계에서 기초적인 생산을 담당하는 플랑크톤류에 미치는 영향에 관해서는 잘 알려져 있지 않다. 본 연구에서는 TBT와 TPT의 분해물인 DBT, MBT, DPT, MPT를 비롯하여 trimethyltin(TMT)과 그분해물인 dimethyltin (DMT)이 기수산 rotifer의 생존에 미치는 독성(96hr-$LC_{50}$)을 조사.비교하였다. 그 결과, DPT(13.8ppb)가 가장 강했으며 TMT(42.9), DBT(80.6), MPT(262.2), MBT와 DMT(>1,000)의 순으로 나타났다. 즉, trialkyltin과 dialkyltin에서는 페닐주석, 부칠주석, 메칠주석의 순으로 독성이 약해지며, mo-noalkyltin에서도 페닐주석화합물이 메칠주석화합물에 비해 독성이 강하다는 것을 확인할 수가 있었다. 이렇듯 독성이 서로 다른 것은 유기주석화합물의 소수성(lipo-philicity)과도 높은 상관이 있었다.

• Biomolecules & Therapeutics
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• 제20권2호
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• pp.207-213
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• 2012

The present study examined the effects of krill-derived phosphatidylserine (Krill-PS) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The rats were administered vehicle (medium-chain triglyceride: MCT) or Krill-PS (50, 100 mg/kg, p.o.) daily for 21 days. The cognitive improving efficacy of Krill-PS in TMT-induced amnesic rats was investigated by assessing the Morris water maze test and by performing choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and cAMP responsive element binding protein (CREB) immunohistochemistry. The rats with TMT injection showed impaired learning and memory of the tasks and treatment with Krill-PS produced a significant improvement of the escape latency to find the platform in the Morris water maze at the $2^{nd}$ and $4^{th}$ day compared to that of the MCT group (p<0.05). In the retention test, the Krill-PS+MCT groups showed increased time spent around the platform compared to that of the MCT group. Consistent with the behavioral data, Krill-PS 50+MCT group significantly alleviated the loss of acetylcholinergic neurons in the hippocampus and medial septum compared to that of the MCT group. Treatment with Krill-PS significantly increased the CREB positive neurons in the hippocampal CA1 area as compared to that of the MCT group. These results suggest that Krill-PS may be useful for improving the cognitive function via regulation of cholinergic marker enzyme activity and neural activity.

• 한국식품과학회지
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• 제45권5호
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• pp.661-665
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• 2013

본 연구에서는 국내 대표 밤 품종인 대보(Daebo)의 내피를 활용하여 TMT 유도성 인지 기능 상실에 대한 개선 효과를 연구하였다. 실험에서 각 농도별(5, 10, 20 mg/kg of body weight)로 대보 내피 에틸아세테이트 분획물을 섭취한 mouse를 TMT로 인지기능 손상을 유발하여 Y-maze test와 passive avoidance test한 결과, Y-maze test에서 분획물을 섭취한 group이 TMT 단독 처리군과 비교하였을 때 공간 인지기능을 개선시켰고, passive avoidance test 또한 latency time이 증가한 것으로 나타나 TMT에 의해 유발되는 뇌 신경독성 동물 모델로부터 기억 및 학습능력 개선 효과를 갖는 것으로 확인되었다. 또한 in vivo 동물 실험 후 mouse로부터 적출된 whole brain tissue를 대상으로 ex vivo AChE 활성 및 MDA 함량측정 실험한 결과, 에틸아세테이트 분획물이 TMT효과 대비 AChE의 활성을 일부 유의적으로 억제하는 것을 알 수 있었다. 결론적으로 대보 내피 에틸아세테이트 분획물은 신경전달물질인 AChE의 활성을 저해하고 뇌 신경세포 보호 효과를 통하여 인지기능 개선 효과를 유도할 수 있는 것으로 사료된다.

• 한국식품과학회지
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• 제47권3호
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• pp.373-379
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• 2015

본 연구에서는 들기름의 TMT 유도성 인지 기능 상실에 대한 개선 효과와 함께 가정에서 식용유로서 사용량이 많은 대두유와 그 효과를 비교 연구하였다. 실험에서 들기름과 대두유를 섭취한 마우스를 TMT로 인지 기능 손상을 유발하여 Y-maze test와 Morris water maze test 한 결과, 공간 인지 기능 및 학습능력 개선에 대해 대두유는 효과가 미비하였으나 들기름은 대조군과 유의적인 차이가 없는 정도의 유의적 개선 효과를 보였다. 동물 실험 후 mouse로부터 적출된 뇌 조직을 대상으로 AChE 활성, MDA 함량, SOD 활성 측정 및 산화된 glutathione 측정한 결과, 대두유는 TMT 단독 처리군의 경우와 유사한 반면 들기름은 TMT에 의해 손상을 입은 mice의 뇌 조직에서 AChE의 활성과 MDA 생성 및 GSH의 산화를 억제시킬 뿐만 아니라 SOD 활성을 유의성 있게 증가시킨 것으로 나타났다. 이러한 결과는 들기름에 존재하는 풍부한 생리 활성 물질로서 ${\omega}$-3계 지방산, 페놀화합물 그리고 비타민 E 등에 의한 것으로 사료된다. 결국 들기름은 상대적으로 우수한 인지 기능 개선 효과를 나타냈고, 이는 건강기능 식품으로서 고부가가치 소재로 활용될 수 있는 산업적 활용 가능성을 나타내는 것으로 판단된다.