• Korean Journal of Veterinary Research
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• v.51 no.3
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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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• v.24 no.3
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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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• v.6 no.2
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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.

• 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.

• Korean Journal of Medicinal Crop Science
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• v.19 no.6
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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.

• Journal of Pharmacopuncture
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• v.20 no.1
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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.

• Korean Journal of Environmental Biology
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• v.21 no.2
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• pp.164-169
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• 2003

Organotins are widely used organometals in various agricultural and industrial purposes. After introduction of these chemicals to the aquatic environment, they are degraded by abiotic and biotic precesses. The triorganotin compounds are sequentially degraded to di-organotin, mono-organotin and then finally inorganic tin. Although the effects of trialkyltin an marine organisms have been intensively studied, little has been known on plankton as a producer of ecosystem. In this paper, the toxicities of dibutyltin (DBT), monobutyltin (MBT), diphenyltin (DPT), monophenyltin (MPT), trimethyltin (TMT) and dimethyltin (DMT) to rotifer Brachionus plicatilis were measured, and their potencies were compared based on 96 hr-$LC_{50}$ value. The results showed that DPT (13.8 ppb) was the highest toxic, which was followed by TMT (42.9), DBT (80.6), MPT (262.2), MBT and DMT (>1,000) in order. Thus, in tri- and diorganotins, the toxicity was observed phenyltins > butyltins > methyltins, and in mono-organotins phenyltins was more toxic than butyltins. Considering the order of 96 hr--$LC_{50}$ with octanol-water eoefficients ($K_{ow}$) in organotins together, it was considered that the toxicity of organotins seems to be related to the lipophilicity of the compounds.

• Biomolecules & Therapeutics
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• v.20 no.2
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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.

• 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.

• Korean Journal of Food Science and Technology
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• v.47 no.3
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• pp.373-379
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• 2015

This study aimed to investigate the anti-amnesic effect of perilla oil against trimethyltin (TMT)-induced learning and memory impairment in ICR mice. Perilla oil (2.5 mL/kg of body weight) and soybean oil (2.5 mL/kg of body weight) were administered orally to mice for 3 weeks, and at the end of the experimental period, cognitive behavior was examined by Y-maze and Morris water maze (MWM) tests. Behavioral tests showed that the mice treated with perilla oil had improved cognitive function compared to that in mice administered soybean oil. Analysis of brain tissue showed that perilla oil significantly lowered acetylcholinesterase activity and malondialdehyde (MDA) levels. Oxidized glutathione (GSH)-to-total GSH ratio also decreased from 10.4% to 5.3% in perilla oil-treated mice, but superoxide dismutase (SOD) activity increased from 11.7 to 14.2 U/mg protein. Therefore, these results suggest that the perilla oil could be a potential functional substance for improving cognitive function.