Cerebral endothelial cell and Neurotrophins

脑内皮细胞和神经营养素

• 批准号: 13671177
• 负责人: TATSUNO Ichiro
• 金额: $ 1.73万
• 依托单位: CHIBA 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-13671177/
• 关键词: Cerebral Endothelial cell; Oxidozed LDL; Neurotrophin; Neurotrophin Receptor; Proliferation; NO; PACAP; Cross-talk

Cerebral endothelial cells (CEC) are one of the major and key components for formation of the vascular system in the mammalian central nervous system (CNS), which is characteristic and different from that in other organs in terms of the formation of the blood-brain barrier (BBB). Although it has been clarified that both formation and maintenance of the vascular system in CNS are dependent on the cross-talk between neuronal cells and vascular endothelial cells, the precise mechanism is still being investigated. In this regard, we focused on the neurotrophin (NT) produced by neuronal cells for its possible involvement in signaling for the regulation of CEC in comparison of rat cerebral endothelial cells (RCEC) with rat aortic endothelial cells (RAEC). We found that 1) trk C, a receptor for neurotrophin-3 (NT-3), is dominantly expressed in RCEC, but trk B, a receptor for brain-derived neurotrophic factor (BDNF), is dominantly expressed in RAEC ; 2) NT-3 inhibited the proliferation of RCEC ; and 3) NT-3 stimulated the production of nitric oxide (NO) with increases in protein expression of endothelial NO synthase (eNOS). These data indicated that NT may regulate and/or maintain the functions of the brain microvasculature through the regulation of CEC.

脑内皮细胞（cerebral endothelial cells，CEC）是哺乳动物中枢神经系统（central nervous system，CNS）血管系统形成的主要和关键成分之一，其血脑屏障（blood-brain barrier，BBB）的形成具有特征性，不同于其他器官。虽然已经阐明CNS中血管系统的形成和维持都依赖于神经元细胞和血管内皮细胞之间的串扰，但确切的机制仍在研究中。在这方面，我们集中在神经元细胞产生的神经营养因子（NT），其可能参与的信号调节CEC的比较，大鼠脑血管内皮细胞（RCEC）和大鼠主动脉内皮细胞（RAEC）。结果发现：1）神经营养素-3（NT-3）受体trk C在RCEC中占优势表达，而脑源性神经营养因子（BDNF）受体trk B在RAEC中占优势表达; 2）NT-3抑制RCEC增殖; 3）NT-3刺激一氧化氮（NO）的产生，同时增加内皮型NO合成酶（eNOS）的蛋白表达。提示NT可能通过调节CEC来调节和/或维持脑微血管功能。

项目成果

Ichiro Tatsuno: "PACAP is an anti-mitogenic signal in developing cerebral cortex"Nature Neuroscience. 4. 123-124 (2001)

Ichiro Tatsuno：“PACAP 是大脑皮层发育过程中的一种抗有丝分裂信号”《自然神经科学》。

Ichiro Tatsuno: "Anterior ischemic optic neuropathy associated with idiopathic aldosteronism and hypertension"Opthalmologia. 216. 68-70 (2002)

Ichiro Tatsuno：“与特发性醛固酮增多症和高血压相关的前部缺血性视神经病变”Opthalmologia。

Yamada N, Kaneko K, Saito Y, Tatsuno I: "Anticonvulsant hypersensitivity syndrome with marked eosinophilia in treatment of diabetic neuropathy"Diabetes Care. 25. 1099-1100 (2002)

Yamada N、Kaneko K、Saito Y、Tatsuno I：“治疗糖尿病神经病变时伴有明显嗜酸性粒细胞增多的抗惊厥过敏综合征”糖尿病护理。

Sakashita Y, Kurihara T, Uchida D, Tatsuno I, Yamamoto T: "Involvement of PACAP receptor in primary afferent fiber-evoked responses of ventral roots in the neonatal rat spinal cord"Br J Pharmacol. 132. 1769-1776 (2001)

Sakashita Y、Kurihara T、Uchida D、Tatsuno I、Yamamoto T：“PACAP 受体参与新生大鼠脊髓腹侧根的初级传入纤维诱发反应”Br J Pharmacol。

Suh J, Lu N, Nicot A, Tatsuno I, DiCicco-Bloom E: "PACAP is an anti-mitogenic signal in developing cerebral cortex"Nature Neuroscience. 4. 123-124 (2001)

Suh J、Lu N、Nicot A、Tatsuno I、DiCicco-Bloom E：“PACAP 是大脑皮层发育中的抗有丝分裂信号”《自然神经科学》。