Elucidation of the mechanisms of the impairment of functional neuron networks and establishment of the therapeutic strategies.

阐明功能神经网络损伤的机制并建立治疗策略。

• 批准号: 08407007
• 负责人: NAGAO Seigo
• 金额: $ 22.02万
• 依托单位: Kagawa Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08407007/
• 关键词: calcium; Cdk5; p35; neuronal cell; calbrain; kindlling; ischemic neuronal death; ecalectin; calmodulin-dependent enzyme; 成長ホルモン; 脳血管関門; 老化促進モデルマウス; RU-51599; リンホカイン; カルモジュリン依存性リン酸化酵素; 長期記憶増強; Calbrain; タウ; 網膜

1. Anti-allergic drugs such as amlexanox and cromolyn bound to S-100, visin-like protein, and 14-3-3, and inhibited their functions.2. During the developmental processes of rat brain, the expression level of cyclin-dependent kinase 5 (Cdk5) did not alter, and its activaot, p35, did.3. Calmodulin-dependent protein kinases (CaMK) I and IV were involved in the formation of long-term potentiation using rat hippocampal slices. A novel calcium-binding protein, calbrain, inhibited CaMK II.4. Using a calcineurin-specific inhibitor, FK506, calcineurin was shown to be involved in the epileptogenesis of the kindled rats.5. By the study using SAM (Senescence-Accelerated Mouse), the impairment of blood-brain barrier was shown to occur during the aging processes.6. The hypothermic treatment worked effectively to protect the delayed neuronal death after the brain ischemia. It was important to raise the body temperature to the normal level as slow as possible after this therapy.7. Neuronal transplantation of fetal hippocampal cells induced the recovery of the memory and learning impaired rats.8. Transcription and translation of growth hormone was enhanced by the inhibition of calcineurin using immunosuppressive drugs (FK506 and cyclosporin A).

1.抗过敏药物氨来占诺、克罗埃宁等与S-100、visin样蛋白、14-3-3结合，抑制其功能.在大鼠脑发育过程中，细胞周期蛋白依赖性激酶5（Cdk 5）的表达水平没有发生变化，而其激活因子p35的表达水平发生了变化.钙调素依赖性蛋白激酶（CaMK）I和IV参与使用大鼠海马脑片的长时程增强的形成。一种新的钙结合蛋白，calbrain，抑制CaMK II. 4。使用钙调神经磷酸酶特异性抑制剂FK 506，钙调神经磷酸酶被证明参与点燃大鼠的癫痫发生。通过SAM（Senescence-Accelerated Mouse）的研究发现，衰老过程中存在血脑屏障的损伤.低温治疗对脑缺血后迟发性神经元死亡有明显的保护作用。重要的是，在这种治疗后，尽可能缓慢地将体温升高到正常水平。胎鼠海马神经元移植可促进大鼠学习记忆功能的恢复.使用免疫抑制药物（FK 506和环孢菌素A）抑制钙调神经磷酸酶可增强生长激素的转录和翻译。

项目成果

Akiyoshi Moriwaki et al.: "Immunosuppressant FK506 prevents mossy fiber sprouting induced by kindling stimulation." Neuroscience Research. 25. 191-194 (1996)

Akiyoshi Moriwaki 等人：“免疫抑制剂 FK506 可防止引火刺激引起的苔藓纤维发芽。”

A.Moriwaki: "Immunosuppressant FK506 prevents mossy fiber sprouting induced by kindling stimulation." Neuroscience Research. 25. 191-194 (1996)

A.Moriwaki：“免疫抑制剂 FK506 可防止引火刺激引起的苔藓纤维发芽。”

M.Ueno: "Age related changes in the brain transfer of blood-borne horseradish peroxidase in the hippocampus of senescence-accelerated mouse." Acta Neuropatholgy. 93. 233-240 (1997)

M.Ueno：“衰老加速小鼠海马体中血源性辣根过氧化物酶脑转移的年龄相关变化。”

Q.Xie: "Evaluation of pulmonary afferent fibers in the nucleus tractus solitarius : a horseradish peroxidase and c-fos like immunohistochemical study in the rat" J.Auton.Nerv.Sys.74. 120-125 (1998)

Q.Xie：“孤束核中肺传入纤维的评估：大鼠中的辣根过氧化物酶和 c-fos 样免疫组织化学研究”J.Auton.Nerv.Sys.74。

A.Moriwaki et al.: "Immunosuppressant FK506 prevents mossy fiber sprouting induced by kindling stimulation." Neuroscience Research. 25. 191-194 (1996)

A.Moriwaki 等人：“免疫抑制剂 FK506 可防止引火刺激引起的苔藓纤维发芽。”