Association of leptomeningeal and glial cells in the persistent pain

软脑膜细胞和神经胶质细胞在持续性疼痛中的关联

• 批准号: 18613010
• 负责人: TAKE Hiro
• 金额: $ 2.61万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18613010/
• 关键词: pain; leptomeninges; inflammatory cytokines; glial cells; patch clamp; NMDA receotors; パッチクランプ; 三叉神経脊髄路核; 下歯槽神経切断; アストロサイト

After immunization with the complete Freund's adjuvant (CFA) , cyclooxygenase (COX) -2 and membrane-bound prostaglandin E synthase-1 (mPGES-1) were induced in the leptomeninges. Primary cultured leptomeningeal cells secreted PGE_2 after treatment with lipopolysaccharide (LPS) or proinflammatory cytokines. The LPS-induced release of PGE_2 was depressed by a selective COX-2 inhibitor, NS-398. On the other hand, TGF-β1 and TGF-β receptor II(TGF-βRII)both markedly increased in the leptomeninges and the parenchymal cells after the CFA injection. Double staining immunohistochemistry demonstrated TGF-β1 to be induced in both glial cells and cortical neurons, while TGF-βRII was only induced in cortical neurons. PGE_2 was found to directly increase the production of TGF-β1 and TGF-βRII in the primary cultured cells. These observations strongly suggest that PGE_2, which is biosynthesized by the leptomeninges, mainly regulates the production of TGF-β1 by glial cells and cortical neuron, thus playing a protective role in the cortical neurons during systemic inflammation. Furthermore, we found that IL-1β increased the neuronal excitability by inhibition of ChTX-sensitive K^ca channels activated by Ca^ (2+) influx through both NMDA receptors and voltage-gated Ca^ (2+) channels, contributing to the pathogenesis of persistent pain.

用完全弗氏佐剂（CFA）免疫后，在软脑膜中诱导环氧合酶（考克斯）-2和膜结合前列腺素E合成酶-1（mPGES-1）。原代培养的软脑膜细胞经脂多糖（LPS）或促炎细胞因子处理后可分泌PGE_2。选择性考克斯-2抑制剂NS-398可抑制LPS诱导的PGE_2释放。另一方面，注射CFA后，软脑膜和实质细胞中的TGF-β1和TGF-β受体II（TGF-βRII）均显著增加。免疫组化双染显示TGF-β1在胶质细胞和皮质神经元中均有表达，而TGF-βRII仅在皮质神经元中表达。PGE_2可直接促进原代培养细胞TGF-β1和TGF-β R Ⅱ的产生。提示PGE_2主要通过调节胶质细胞和皮层神经元产生TGF-β_1，在全身炎症反应中对皮层神经元起保护作用。此外，我们发现IL-1β通过抑制ChTX敏感性K^ca通道而增加神经元兴奋性，该通道由通过NMDA受体和电压门控Ca^2+通道的Ca^2+内流激活，参与了持续性疼痛的发病机制。

项目成果

Systemic inflammation induces age-dependent defferential activation ofglial cells through the leptomeninges

全身炎症通过软脑膜诱导神经胶质细胞的年龄依赖性差异激活

• 发表时间: 2007
• 作者: Wu Z.;Nakanishi H.;Wu Z. and Nakanishi H.
• 通讯作者: Wu Z. and Nakanishi H.

Age-dependent differential activation profiles of glial cells by theleptomeninges during systemic inflammation:In NeuroimmunologyResearch Focus, (Broglio PV ed)

全身炎症过程中软脑膜对神经胶质细胞的年龄依赖性差异激活特征：神经免疫学研究焦点，（Broglio PV ed）

• 发表时间: 2007
• 作者: Wu Z.;Nakanishi H.(分担)
• 通讯作者: Nakanishi H.(分担)

Involvement of COX-1 and up-regulated prostaglandin E synthases inphosphatidylserine liposome-induced PGE2 production of microglia

COX-1 和上调的前列腺素 E 合酶参与磷脂酰丝氨酸脂质体诱导的小胶质细胞 PGE2 产生

• 发表时间: 2006
• 期刊: Journal of Neuroimmunology 172
• 作者: Zhang J.;et. al.
• 通讯作者: et. al.

Potentiation of NMDA receptor-medoated responses through ativation of the glycine site by microglia secreting soluble factor.

通过小胶质细胞分泌可溶性因子激活甘氨酸位点来增强 NMDA 受体介导的反应。

• 发表时间: 2006
• 期刊: Glia 53
• 作者: Hayashi;Y.;Ishibashi;H.;Hashimoto;K.;Nakaniihi;H
• 通讯作者: H

Microglial Proteases: In Neural Protein Metabolism & Function. Handbookof Neurochemistry and Molecular Neurobiology, vol.7 (Lajtha A ed)

小胶质细胞蛋白酶：在神经蛋白质代谢中

• 发表时间: 2007
• 作者: Hayashi;Y.;Suzuki;H.;Sawada;M.;Nakanishi;H;中西 博;Wu Z. and Nakanishi H.(分担);Nakanishi H.(分担)
• 通讯作者: Nakanishi H.(分担)