INCREASE IN OMEGA-3 (PERIPHERAL TYPE BENZODIAZEPINE) BINDING-SITES IN THE RAT CORTEX AND STRIATUM AFTER LOCAL INJECTION OF INTERLEUKIN-1, TUMOR-NECROSIS-FACTOR-ALPHA AND LIPOPOLYSACCHARIDE
INCREASE IN OMEGA-3 (PERIPHERAL TYPE BENZODIAZEPINE) BINDING-SITES IN THE RAT CORTEX AND STRIATUM AFTER LOCAL INJECTION OF INTERLEUKIN-1, TUMOR-NECROSIS-FACTOR-ALPHA AND LIPOPOLYSACCHARIDE
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DOI：
10.1016/0006-8993(91)90028-t
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发表时间：
1991-03-15
期刊：
影响因子：
2.9
通讯作者：
SCATTON, B
中科院分区：
文献类型：
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作者：
BOURDIOL, F;TOULMOND, S;SCATTON, B
通过在大鼠大脑皮层和纹状体局部注射淋巴因子后测量与神经胶质细胞和巨噬细胞相关的omega-3（外周型苯二氮卓类）结合位点的密度，研究了淋巴因子在脑损伤后神经胶质反应/增殖中的可能参与。 通过脑切片中的定量放射自显影或通过使用[H-3]PK 14105或[H-3]PK 11195作为配体的膜中的常规结合来测量ω-3位点密度。 注射后7天，皮质内或纹状体内输注白细胞介素-1（10和20单位）导致注射部位周围omega-3位点密度显著增加（与盐水输注动物相比，分别为+83%和+80%）。 omega-3位点的放射自显影分布与反应性星形胶质细胞（通过GFAP免疫染色评估）或富含酸性磷酸酶的细胞（吞噬细胞）的分布之间存在良好的空间对应性。 局部给予肿瘤坏死因子-α（TNF-α）后1周，在纹状体匀浆中也观察到omega-3位点密度显著增加。 在给予3个单位后观察到最大增加（+80%），较高和较低剂量导致较小的增加。 纹状体内注射E.大肠杆菌脂多糖（LPS），一种已知刺激培养物中小胶质细胞产生白细胞介素-1和TNF-α的细菌内毒素，也导致纹状体匀浆中ω-3位点密度的显著增加（最大增加，注射200 ng后1周+170%）。 相比之下，在纹状体内注射白细胞介素-1、TNF-α或LPS后，观察到与神经元相关的两个结合位点（[H-3]TCP，其指示NMDA受体密度;[H-3] Ro 15 1788，其结合中央omega-1-2（苯二氮卓类）受体）的密度没有变化。 纹状体内注射白细胞介素-2（5-20单位）或趋化肽N-甲酰-甲硫氨酰-亮氨酰-苯丙氨酸（FMLP）未能改变纹状体匀浆中的omega-3位点或NMDA受体密度。 基于目前的结果，我们认为，在实验性病变和人类神经病理状态中观察到的omega-3位点密度的增加可能是介导的一个顺序机制，涉及小胶质细胞或单核细胞的激活，白细胞介素-1和/或TNF-α的释放和促进，由这些细胞因子，星形胶质细胞反应。
The possible involvement of lymphokines in the glial reaction/proliferation that follows brain injury has been investigated by measuring the density of omega-3 (peripheral type benzodiazepine) binding sites associated to glial cells and macrophages after local injection of lymphokines in the rat cerebral cortex and striatum. Omega-3 site densities were measured either by quantitative autoradiography in brain sections or by conventional binding in membrane using [H-3]PK 14105 or [H-3]PK 11195 as ligands. Intracortical or intrastriatal infusion of interleukin-1 (10 and 20 units) caused a marked increase in the density of omega-3 sites (+83% and +80%, respectively, when compared to saline-infused animals) around the injection site at 7 days postinjection. There was a good spatial correspondence between the autoradiographic distribution of omega-3 sites and the distribution of reactive astrocytes (as assessed by GFAP immunostaining) or acid phosphatase rich cells (phagocytes). Significant increases in omega-3 site densities were also observed in striatal homogenates 1 week after local administration of tumor necrosis factor-alpha (TNF-alpha). The maximal increase (+80%) was observed after the administration of 3 units, higher and lower doses resulting in smaller increases. Intrastriatal injection of E. coli lipopolysaccharide (LPS), a bacterial endotoxin known to stimulate interleukin-1 and TNF-alpha production by microglial cells in culture, also resulted in significant increases in omega-3 site densities in striatal homogenates (maximal increase, +170% 1 week after the injection of 200 ng). In contrast, no change in the density of two binding sites associated with neurons ([H-3]TCP which indexes NMDA receptor density and [H-3]Ro15 1788 which binds to central omega-1-2 (benzodiazepine) receptors) was observed after intrastriatal injection of interleukin-1, TNF-alpha or LPS. The intrastriatal injection of interleukin-2 (5-20 units) or of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) failed to alter omega-3 site or NMDA receptor densities in striatal homogenates. Based on the present results, we suggest that the increase in omega-3 site densities observed in experimental lesions and in human neuropathological states may be mediated by a sequential mechanism involving the activation of microglia or monocytes, the release of interleukin-1 and/or TNF-alpha and the promotion, by these cytokines, of the astroglial reaction.