EXPERIMENTAL PHARMACOLOGICAL STUDY OF DEMENTIA MODEL ANINAL

痴呆模型动物的药理实验研究

• 批准号: 62480248
• 负责人: MIYOSHI Koho
• 金额: $ 1.98万
• 依托单位: Hyogo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-62480248/
• 关键词: Dementia; Acetylcholine; Nucleus basalis magnocellularis; Passive avoidance; Cholinesterase inhibitor; THA; NIK-247; THA; NIKー247; 痴呆モデル動物; 回避学習能力; フィゾスチグミン; フィゾスティグミン

The nucleus basalis magnocellularis(NBM) of the rat is homologous to the human nucleus basalis of Meynert, which implicated in the cholinergic hypothesis of cognitive impairment in Alzheimer's disease. The excitotoxin kainic acid or ibotenic acid was used to produce unilateral lesions in NBM of rats. CAT activity, and Ach decreased and binding of ^3H-QNB increased in lesioned side of cerebral cortex. Decrease of AchE, reactivity occurred in the cortex of lesioned side. Neuronal loss was observed in the cerebral cortex one and half year after the NBM lesion. Neither neurofibrillary tangles nor senile plaques was visible in the cerebral cortex of lesioned animals.Compared with sham-operated controls,the NBM lesioned rats exhibited a impairment of acquisition and retention of passive avoidance response.THA or NIK-247 administration produced a significant increase of Ach in the cerebral Cortex, and ameliorated memory disturbance of the NBM-lesioned rats.Continuous injection of Ach or choline with osmic pump during 14 days showed ameriolating effect of memory disturbance of the animal model.

大鼠的大细胞基底核（NBM）与迈纳特的人类基底核同源，这与阿尔茨海默病认知障碍的胆碱能假说有关。使用兴奋毒素红藻氨酸或鹅膏蕈酸在大鼠 NBM 中产生单侧损伤。在大脑皮层病变侧，CAT 活性和 Ach 降低，^3H-QNB 结合增加。病侧皮质AchE、反应性降低。 NBM 损伤一年半后，在大脑皮层观察到神经元损失。病变动物的大脑皮层中既没有可见的神经原纤维缠结，也没有出现老年斑。与假手术对照组相比，NBM病变大鼠表现出被动回避反应的获得和保留受损。THA或NIK-247给药使大脑皮层中的Ach显着增加，并改善了记忆障碍。 NBM损伤大鼠。用渗透泵连续注射乙酰胆碱或胆碱14天，对动物模型的记忆障碍有改善作用。

项目成果

Miyoshi, K.Takauchi, S.Ueki, A.Taira, H.Furuhasi, A.Sato, M.: "Neuropathological changes of the cerebral cortex in ventral globus pallidus lesioned rat." Ann.Rep.Pharmacopsychiat.Res.Found. 20, 10-20, 1989.

Miyoshi，K.Takauchi，S.Ueki，A.Taira，H.Furuhasi，A.Sato，M.：“腹侧苍白球病变大鼠大脑皮层的神经病理变化。”

Miyoshi, K.Ueki, A.: "Receptor and disease.Alzheimer's disease." Clinical Neuroscience.8, 64-65, 1990.

Miyoshi, K.Ueki, A.：“受体与疾病。阿尔茨海默病。”

三好功峰: "老年期の痴呆;患者さんの心を理解しよう" 有斐閣, 1-209 (1988)

三好晃帆：“老年痴呆症：让我们了解患者的想法” Yuhikaku，1-209 (1988)

Ueki.A;Miyoshi.K: The Japanese Journal of Psychiatry and Neurology. 41. 77-85 (1987)

Ueki.A；Miyoshi.K：日本精神病学和神经病学杂志。

Ueki A.: "Changes in cholinergic markers following kainic acid lesions of ventral globus pallidus in rats." Jap J Psychiat Neurol. 41. 87-96 (1987)

Ueki A.：“大鼠腹侧苍白球红藻氨酸损伤后胆碱能标志物的变化。”