The p38 mitogen-activated protein kinase inhibitor SB203580 antagonizes the inhibitory effects of interleukin-1β on longterm potentiation in the rat dentate gyrus in vitro
The p38 mitogen-activated protein kinase inhibitor SB203580 antagonizes the inhibitory effects of interleukin-1β on longterm potentiation in the rat dentate gyrus in vitro
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DOI：
10.1016/s0306-4522(99)00100-1
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发表时间：
1999-01-01
期刊：
影响因子：
3.3
通讯作者：
O'Connor, JJ
中科院分区：
文献类型：
--
作者：
Coogan, AN;O'Neill, LAJ;O'Connor, JJ
已知促炎细胞因子白细胞介素-1 β的水平在患有慢性疾病如阿尔茨海默病的患者中升高。我们研究了白细胞介素-1 β对长时程增强和N-甲基-D-天冬氨酸受体介导的场电位在大鼠齿状回在体外利用场细胞外记录从中间三分之一的分子层的齿状回。突触前刺激施加到连合/协会的途径，在0.05赫兹的频率和距离50 μ m的颗粒细胞体层。如前所述，白细胞介素-1 β（1 ng/ml）可抑制长时程增强（强直刺激后1 h为基线的108 +/- 2%，而溶剂对照切片为145 +/- 5%）。用p38丝裂原相关蛋白激酶抑制剂SB 203580（1 μ M）预处理切片，可减弱白细胞介素-1 β对长时程增强的作用，以及对N-甲基-D-天冬氨酸受体介导的场电位的抑制作用。单独使用SB 203580对长时程增强无显著影响，但确实引起基线突触传递的增加[107 +/-2%基线，SB 203580（1 μ M）处理后1小时]。p42/44丝裂原活化蛋白激酶级联抑制剂PD 98059（50 μ M）不能抑制白细胞介素-1 β诱导的N-甲基-D-天冬氨酸受体介导的场电位抑制。环氧合酶抑制剂吲哚美辛（50 μ M）被发现减弱白细胞介素-1 β诱导的长时程增强和N-甲基-D-天冬氨酸受体介导的场电位的影响。发现脂质第二信使类似物C2神经酰胺（20 μ M）减弱长时程增强的表达（强直刺激后1小时为基线的108 +/- 3%），并且这种作用未被SB 203580预处理阻断。为了研究白细胞介素-1 β在长时程增强的正常表达中的可能作用，在长时程增强的维持阶段期间应用白细胞介素-1受体拮抗剂（25 ng/ml）。这被发现抑制了长时程增强的持续表达（强直刺激后1小时基线的116+/-6%h.）。我们的研究结果表明，病理生理浓度的白细胞介素-1 β可能有助于抑制长时程增强的信号传导机制，也表明IL-1 β在体外大鼠齿状回突触可塑性的生理表达中的作用。(C)1999年IBRO。出版社：Elsevier Science Ltd
Levels of the pro-inflammatory cytokine interleukin-1 beta are known to be elevated in patients with chronic disorders such as Alzheimer's disease. We have investigated the effects of interleukin-1 beta on long-term potentiation and N-methyl-D-aspartate receptor-mediated field potentials in the rat dentate gyrus in vitro utilizing field extracellular recordings obtained from the middle third of the molecular layer of the dentate gyrus. Presynaptic stimulation was applied to the commissural/association pathway at a frequency of 0.05 Hz and at a distance of 50 mu m from the granule cell body layer. As previously reported, interleukin-1 beta (1 ng/ml) caused an inhibition of long-term potentiation (108 +/- 2% of baseline 1 h following application of tetanic stimulation compared with 145 +/- 5% in vehicle control slices). This action of interleukin-1 beta on long-term potentiation, as well as an inhibition of N-methyl-D-aspartate receptor-mediated field potentials, was attenuated by pre-treatment of slices with the p38 mitogen-associated protein kinase inhibitor SB203580 (1 mu M) SB203580 alone had no significant affect on long-term potentiation, but did cause an increase in baseline synaptic transmission [107 +/- 2% of baseline, 1 h after SB203580 (1 mu M) treatment]. The p42/44 mitogen-activated protein kinase cascade inhibitor PD98059 (50 mu M) did not inhibit the interleukin-1 beta-induced inhibition of N-methyl-D-aspartate receptor-mediated field potentials. The cyclooxygenase inhibitor indomethacin (50 mu M) was found to attenuate the interleukin-1 beta-induced effects on both long-term potentiation and N-methyl-D-aspartate receptor-mediated field potentials. The lipid second messenger analogue C2 ceramide (20 mu M) was found to attenuate the expression of long-term potentiation (108 +/- 3% of baseline 1 h following tetanic stimulation), and this effect was not blocked by pre-treatment with SB203580. To investigate a possible role for interleukin-1 beta in the normal expression of long-term potentiation, the interleukin-l receptor antagonist (25 ng/ml) was applied during the maintenance phase of long-term potentiation. This was found to depress the sustained expression of long-term potentiation (116+/-6% of baseline 1 h following tetanic stimulation).Our results indicate possible signalling mechanisms by which interleukin-1 beta at pathophysiological concentrations may serve to inhibit long-term potentiation, and also suggests a role for IL-1 beta in the physiological expression of synaptic plasticity in the rat dentate gyrus in vitro. (C) 1999 IBRO. Published by Elsevier Science Ltd.