Research on the common signal transduction bases of mood, motivation and memory related disorders

情绪、动机和记忆相关疾病常见信号转导基础的研究

• 批准号: 11670956
• 负责人: OZAWA Hiroki
• 金额: $ 1.73万
• 依托单位: Sapporo 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: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670956/
• 关键词: Mood disorder; schizophrenia; postmortem human brain; G protein; membrane environment; second messengers; Alzheimer disease; signal transduction; cAMP; アデニル酸シクラーゼ; ホスホリパーゼC; CREB

Affective disorder and schizophrenia are the two most important endogenous psychiatric diseases. Recently several researchers have suggested that there are common and overlapping symptoms between these two disorders, especially in terms of depression and negative symptoms of schizophrenia.. We examined the productive activity of two second messengers systems [adenylyl cyclase (AC) activity phospholipase C (PLC)] in membrane preparations from postmortem frontal cortex of monopolar depressive patients and chronic schizophrenia in comparison with control subjects. Basal AC activity was significantly decreased in depressives, and Mn^<2+>-stimulated AC activity had a tendency to decline compared to controls. In contrast to depressions, there were no differences in basal and Mn^<2+> stimulated AC activity between schizophrenia and controls. In the other hand, 5-HT-stimulated PLC activity as significantly increased in both depressives and schizophrenia compared to controls. Additionally, the immunoreactivities of AC-I and AC-II subtypes showed significant decreases in Alzheimer disease brains compared to controls. These results indicated that the impairment in productive activity of second messengers is related to the pathophysiology of depression, schizophrenia and Alzheimer disease related with of mood, motivation and memory disturbances.

情感性障碍和精神分裂症是两种最重要的内源性精神疾病。最近，一些研究人员提出，这两种疾病之间存在共同和重叠的症状，特别是在抑郁症和精神分裂症的阴性症状方面。我们检测了单极抑郁症患者和慢性精神分裂症患者死后额叶皮层膜制剂中两种第二信使系统[腺苷酸环化酶（AC）活性磷脂酶C (PLC)]的产生活性，并与对照组进行了比较。抑郁症患者的基础AC活性显著降低，与对照组相比，Mn^<2+>刺激的AC活性有下降的趋势。与抑郁症相比，精神分裂症和对照组在基础和Mn^<2+>刺激的AC活性方面没有差异。另一方面，与对照组相比，5- ht刺激的PLC活性在抑郁症和精神分裂症患者中均显著增加。此外，与对照组相比，ac - 1和AC-II亚型的免疫反应性在阿尔茨海默病患者的大脑中显着降低。这些结果表明，第二信使生产活性的损害与抑郁症、精神分裂症和阿尔茨海默病的病理生理有关，与情绪、动机和记忆障碍有关。

项目成果

Yamamoto-Sasaki M, Ozawa H et al.: "Impaired phosphorylation of cyclic AMP response element binding protein in the hippocampus of the Alzheimer type"Brain Res. 824. 300-303 (1999)

Yamamoto-Sasaki M、Ozawa H 等人：“阿尔茨海默型海马中环 AMP 反应元件结合蛋白的磷酸化受损”Brain Res。

Ozawa H et al.: "Tranzodone and second messengers system"Progress in Medicine. 19. 2553-2356 (1999)

小泽H等：“曲佐酮和第二信使系统”医学进展。

Rasenick,MM.,Chen J and Ozawa H: "In Bipolar Medications.mechanismss of action.ed.Husseini K.Manii, Charles L.Bowden and Robert H.Belmaker"American Psychiatric Press, Washington, DC. 87-108 (1999)

Rasenick,MM.、Chen J 和 Ozawa H：“双相药物治疗。作用机制。ed.Husseini K.Manii、Charles L.Bowden 和 Robert H.Belmaker”美国精神病学出版社，华盛顿特区。

小澤寛樹 ら: "トラゾドンと2次メッセンジャー系について"Progress in Medicine. 19. 2553-2355 (1999)

Hiroki Ozawa 等人：“曲唑酮和第二信使系统”医学进展 19. 2553-2355 (1999)。

鵜飼渉,小澤寛樹 ら: "脳機能改善薬アニラセタム慢性投与後の線条体cAMP産生能とアデニル酸シクラーゼ発現変化"脳の科学. 21. 297-301 (1999)

Wataru Ukai、Hiroki Ozawa 等人：“长期服用脑功能改善药物阿尼西坦后纹状体 cAMP 产生和腺苷酸环化酶表达的变化”《脑科学》21. 297-301 (1999)。