Translocator protein (18 kDa) is involved in the regulation of reactive gliosis
Translocator protein (18 kDa) is involved in the regulation of reactive gliosis
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DOI：
10.1002/glia.20558
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发表时间：
2007-11-01
期刊：
影响因子：
6.2
通讯作者：
Garcia-Segural, Luis Miguel
中科院分区：
文献类型：
--
作者：
Veiga, Sergio;Carrero, Paloma;Garcia-Segural, Luis Miguel
转运蛋白(18 KDa)(TSPO)是线粒体通透性转运孔的重要组成部分，以前被称为外周型苯二氮卓类受体。脑部炎症可诱导神经胶质细胞表达TSPO，某些TSPO配体可抑制脑损伤后反应性胶质细胞增生。然而，由于一些TSPO配体具有神经保护作用，它们对反应性胶质细胞增生症的影响可能是神经退行性变减少的结果。为了评估TSPO配体是否能够在没有神经元死亡的情况下调节反应性胶质细胞增生，我们测试了它们对内毒素(LPS)侧脑室注射诱导的雄性大鼠海马炎性反应的影响。荧光Jade-B染色显示，脂多糖处理不能诱导神经元死亡，但增加了作为反应性星形胶质细胞和反应性小胶质细胞标记物的Vimentin和MHC-II免疫阳性细胞的数量。此外，内毒素还可使增殖的小胶质细胞数量增加。TSPO配体PK11195可减少脂多糖诱导的MHC-II免疫反应细胞数和小胶质细胞的增殖。相反，另一种TSPO配体Ro5-4864对小胶质细胞对内毒素的反应没有显著影响。在研究的时间点，PK11195和Ro5-4864都不影响内毒素诱导的波形蛋白免疫反应阳性星形胶质细胞的数量的增加，尽管PK11195降低了波形蛋白的免疫反应。这些发现确认TSPO是控制神经炎症的潜在目标，表明TSPO配体PK11195可能通过一种独立于神经元存活调节的机制减少小胶质细胞的激活。(C)2007年Wiley-Liss，Inc.
Translocator protein (18 kDa) (TSPO), previously known as peripheral-type benzodiazepine receptor, is a critical component of the mitochondrial permeability transition pore. Brain inflammation results in the induction of the expression of TSPO in glial cells and some TSPO ligands decrease reactive gliosis after brain injury. However, since some TSPO ligands are neuroprotective, their effects on reactive gliosis may be the consequence of a reduced neurodegeneration. To assess whether TSPO ligands can modulate reactive gliosis in absence of neuronal death, we have tested their effects on the inflammatory response induced in the hippocampus of male rats by the intracerebroventricular infusion of lipopolysaccharide (LPS). LPS treatment did not induce neuronal death, assessed by Fluoro jade-B staining, but increased the number of cells immunoreactive for vimentin and MHC-II, used as markers of reactive astrocytes and reactive microglia, respectively. Furthermore, LPS produced an increase in the number of proliferating microglia. The TSPO ligand PK11195 reduced the number of MHC-II immunoreactive cells and the proliferation of microglia in LPS treated rats. In contrast, another TSPO ligand, Ro5-4864, did not significantly affect the response of microglia to LPS. Neither PK11195 nor Ro5-4864 affected the LPS-mediated increase in the number of vimentin-immunoreactive astrocytes at the time point studied, although PK11195 reduced vimentin immunoreactivity. These findings identify TSPO as a potential target for controlling neural inflammation, showing that the TSPO ligand PK11195 may reduce microglia activation by a mechanism that is independent of the regulation of neuronal survival.(C) 2007 Wiley-Liss, Inc.