• Bulletin of the Korean Chemical Society
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• 제32권spc8호
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• pp.3167-3170
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• 2011

• Toxicological Research
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• 제17권
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• pp.47-57
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• 2001

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, and its pathology is characterized by the presence of numerous numbers of senile plaques and neurofibrillary tangles. Several genetic and transgenic studies have indicated that excess amount of $\beta$-amyloid protein (A$\beta$) is produced by mutations of $\beta$TEX>$\beta$-amyloid precursor protein and causes learning impairment. Moreover, $A\beta$ has a toxic effect on cultured nerve cells. To prepare AD model animals, we have examined continuous (2 weeks) infusion of $A\beta$ into the cerebral ventricle of rats. Continuous infusion of $A\beta$ induces learning impairment in water maze and passive avoidance tasks, and decreases choline acetyltransferase activity in the frontal cortex and hippocampus. Immunohistochemical analysis revealed diffuse depositions of $A\beta$ in the cerebral cortex and hippocampus around the ventricle. Furthermore, the nicotine-evoked release of acetylcholine and dopamine in the frontal cortex/hippocampus and striatum, respectively, is decreased in the $A\beta$-infused group. Perfusion of nicotine (50 $\mu\textrm{M}$) reduced the amplitude of electrically evoked population spikes in the CA1 pyramidal cells of the control group, but not in those of the $A\beta$-infused group, suggesting the impairment of nicotinic signaling in the $A\beta$-infused group. In fact, Kd, but not Bmax, values for ［$^3H$］ cytisine binding in the hippocampus significantly increased in the $A\beta$-infused rats. suggesting the decrease in affinity of nicotinic acetylcholine receptors. Long-term potentiation (LTP) induced by tetanic stimulations in CA1 pyramidal cells, which is thought to be an essential mechanism underlying learning and memory, was readily observed in the control group, whereas it was impaired in the $A\beta$-infused group. Taken together, these results suggest that $A\beta$ infusion impairs the signal transduction mechanisms via nicotinic acetylcholine receptors. This dysfunction may be responsible, at least in part, for the impairment of LTP induction and may lead to learning and memory impairment. We also found the reduction of glutathione- and Mn-superoxide dismutase-like immunoreactivity in the brains of $A\beta$-infused rats. Administration of antioxidants or nootropics alleviated learning and memory impairment induced by $A\beta$ infusion. We believe that investigation of currently available transgenic and non-transgenic animal models for AD will help to clarify the pathogenic mechanisms and allow assessment of new therapeutic strategies.

• Journal of Ginseng Research
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• 제23권2호
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• pp.115-121
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• 1999

에탄올 단기 투여로 유발되는 기억획득의 손상에 대한 홍삼 조 사포닌 성분을 비롯한 수종의 뇌기능개선 후보약물의 급성 및 연속 투여 작용을 검토하였다. 에탄올 급성 투여로 유발된 학습획득 손상 흰쥐에 GABA신경 억제 성 약물인 picrotoxin 급성 투여시 에탄올 투여 흰쥐의 학습획득 손상 작용은 유의성 있는 개선효과를 나타내었으나 diazepam, acetyl-L-carnitine 및 apomoiphie투여 군은 현저한 영향을 미치지 않았다. 급성 홍삼 total saponin 투여군은 에탄올 투여 흰쥐의 학습획득 손상을 유의성 있게 억제하였으며 7일간의 연속 투여에 의해 그 효과가 현저하게 증가하였다. 급성 및 연속 deprenyl투여군은 모두 유의성 있는 억제 작용을 나타내었으나 protopanaxatriol, protopanaxadiol 및 centrophenoxine 투여 군은 모두 현저한 억제작용을 나타내지 않았다. 급성 piracetam 투여 및 연속 N-methyl-D-glucamine투여 군은 유의성 있는 억제효과를 나타내었다. 한편, 에탄올 투여 희쥐의 학습획득 손상에 대한 홍삼 total saponin 연속 투여효과는 ${\alpha}-methyl-전 처치에 의해 유의성 있게 차단되었으나 N-methyl-D-glucamine 연속투여에 의한 억제효과는 부분적으로 차단되었으며, 연속 depreny의 효과는 용량에 따라 차단 또는 증강되는 등 전혀 다른 효과를 나타내었다. 이러한 결과는 에탄올 급성 투여 흰쥐의 학습획득 손상은 picrotoxine, 홍삼 조사포닌, N-methyl-D-glucamme및 deprenyl의 급성 또는 연속 투여가 효과적이며 홍삼 조 사포닌과 N-methyl-D-glucamine 및 deprenyl의 연속 투여 효과는 뇌중 도파민 신경활성에 미치는 영향이 상위함을 나타내고 있다. 따라서 에탄올 급성투여 흰쥐의 학습획득 손상은 일차적으로 뇌중 GABA 신경활성의 억제에 기인하며 이차적으로 도파민신경활성과의 균형의 중요성을 시사하고 있다.