Clinical analysis of neurotoxity in water intoxication and experimental elucidation of its mechanism

水中毒神经毒性的临床分析及其机制的实验阐明

• 批准号: 13671026
• 负责人: KISHIMOTO Toshifumi
• 金额: $ 0.45万
• 依托单位: Nara Medical university
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671026/
• 关键词: water intoxication; neurotoxity; schizophrenia; anti-psychotic drug; apoptosis; 神経毒性

In order to develop the model rats of water intoxication induced by anti-psychotic drug administration, we tried to establish the system of the continuous infusion into the ventricles. First, male Wistar rat of 160-170g were fed for 21 days, and the basic behavioral data were taken. Next, stainless guide-canule was set in SRO under the anesthesia of pentobarbital. Then, saline was continuously injected by osmotic pump through the canule. After 3 weeks, the injection was confirmed by histopathological observations. Thus, the continuous injection system was developed and applied to the examination of water intoxication.And apoptosis of neurons was examined by immunohistological method using anti-caspase 3 antibody that recoginizes the fragmented caspase 3, and by Tunnel staining. These observations showed that some neurons were fallen in apoptotic state even in normal rat brain.Finally, we developed an antibody agaisnt DDB1 which translocates to nucleus at DNA damage, and the observations with the antibody indicated that the apoptotic neurons did not show the DNA repair.

为了建立抗精神病药物致水中毒大鼠模型，我们尝试建立了脑室持续输注系统。首先，雄性Wistar大鼠，体重160~170g，饲养21d，取基础行为学数据。然后，在戊巴比妥钠麻醉下，在SRO置入不锈钢导尿管。然后用渗透泵通过导管持续注入生理盐水。3周后，经组织病理学检查证实注射用药。为此，研制了连续注射系统，并将其应用于水中毒的检测，用识别caspase3片段的抗caspase3抗体的免疫组织化学方法和隧道染色检测神经元的凋亡。这些观察表明，即使在正常大鼠脑内，也有一些神经元处于凋亡状态。最后，我们研制了一种抗DDB1的抗体，该抗体在DNA损伤时移位到细胞核，与该抗体的观察表明，凋亡的神经元没有DNA修复。

项目成果

Hirayama T, Kishimoto T, et al.: "Effect of chronic treatment with haloperidol on vasopressin release and behavioral changes by osmotic stimulation of the supraoptic nucleus"Life Science. 69巻18号. 2147-2156 (2001)

Hirayama T、Kishimoto T 等人：“氟哌啶醇长期治疗对视上核渗透刺激导致的加压素释放和行为变化的影响”，生命科学，第 69 卷，第 18 期。2147-2156 (2001)

Morikawa, M., Kosaka, J., Imai, T., Ohsawa, H., Iida, J., Kishimoto, T.: "A case of general paresis showing marked treatment-associated improvement of cerebellar blood flow by quantitative imaging analysis"Ann.Nucl.Med.. 16. 71-74 (2002)

Morikawa, M.、Kosaka, J.、Imai, T.、Ohsawa, H.、Iida, J.、Kishimoto, T.：“通过定量成像分析，全身性麻痹病例显示治疗相关的小脑血流显着改善

Hirayama, T., Kita, T., Ogawa, Y., Ohsawa, H., Yamashita, M., Nakashima, T., Kishimoto, T.: "Effect of chronic treatment with haloperidol on vasopressin release and behavioral changes by osmotic stimulation of the supraoptic nucleus"Life Sci.. 69. 2147-21

Hirayyama, T.、Kita, T.、Okawa, Y.、Ohsawa, H.、Yamashita, M.、Nakashima, T.、Kishimoto, T.：“氟哌啶醇长期治疗对加压素释放和渗透压行为变化的影响

Morikawa, M., Kosaka, J., Imai, T., Ohsawa, H., Iida, J., Kishimoto, T.: "A case of general paresis showing marked treatment-associated improvement of cerebellar blood flow by quantitative imaging analysis"Ann. Nucl. Med.. 16. 71-74 (2002)

Morikawa, M.、Kosaka, J.、Imai, T.、Ohsawa, H.、Iida, J.、Kishimoto, T.：“通过定量成像分析，全身性麻痹病例显示治疗相关的小脑血流显着改善

Hirayama, T., Kita, T., Ogawa, Y., Ohsawa, H., Yamashita, U., Nakashima, T., Kishimoto, T.: "Effect of chronic treatment with haloperidol on vasopressin release and behavioral changes by osmotic stimulation of the supraoptic nucleus"Life Sci.. 69. 2147-21

Hirayyama, T.、Kita, T.、Okawa, Y.、Ohsawa, H.、Yamashita, U.、Nakashima, T.、Kishimoto, T.：“氟哌啶醇长期治疗对加压素释放和渗透压行为变化的影响