Protection of rat primary hippocampal cultures from Aβ cytotoxicity by pro-inflammatory molecules is mediated by astrocytes
Protection of rat primary hippocampal cultures from Aβ cytotoxicity by pro-inflammatory molecules is mediated by astrocytes
复制标题
DOI：
10.1016/j.nbd.2005.01.007
复制
发表时间：
2005-06-01
影响因子：
6.1
通讯作者：
von Bernhardi, R
中科院分区：
文献类型：
--
作者：
Ramírez, G;Toro, R;von Bernhardi, R
阿尔茨海默病患者的大脑显示大量营养不良的神经突靠近纤维β -淀粉样蛋白（A β）斑块和活化的胶质细胞。我们评估了促炎分子（LPS + ifn - γ）对A β(1-42)神经毒性的影响。2 μ M A β(1-42)诱导海马细胞凋亡，LPS + ifn - γ减少A β诱导的凋亡。然而，LPS + ifn - γ仅在含有星形胶质细胞的海马培养物中阻止细胞凋亡。此外，LPS + ifn - γ仅在含有星形胶质细胞的海马培养物中诱导TGF - β的分泌，TGF - β是一种具有神经保护作用的细胞因子。星形胶质细胞对小胶质细胞和神经元对a的反应具有调节作用。结果表明，传统上被认为是促凋亡的LPS + ifn - γ通过激活星形胶质细胞介导的神经保护机制，减少了a β诱导的细胞凋亡。我们认为星形胶质细胞在中枢神经系统炎症的调节中起关键作用。激活的星形胶质细胞的调节功能受损可能是神经退行性疾病的重要致病机制。(c) 2005爱思唯尔公司版权所有。
The brain of Alzheimer's disease patients shows abundant dystrophic neurites in close proximity to fibrillar beta-amyloid (A beta) plaques, and activated glial cells. We evaluated the influence of pro-inflammatory molecules (LPS + IFN-gamma) on A beta(1-42) neurotoxicity. 2 mu M A beta(1-42) induced apoptosis of hippocampal cells and LPS + IFN-gamma reduced the apoptosis induced by A beta. However, LPS + IFN-gamma prevented apoptosis only in hippocampal cultures containing astrocytes. Also, LPS + IFN-gamma induced the secretion of TGF beta, a cytokine having neuroprotective effects, only in hippocampal cultures that contained astrocytes. Astrocytes had a regulatory effect over microglial and neuronal responses to A. The results suggest that LPS + IFN-gamma, traditionally considered as pro-apoptotic, reduced apoptosis induced by A beta through the activation of neuroprotective mechanisms mediated by astrocytes. We propose that astrocytes are pivotal in the modulation of inflammation of the CNS. The impairment of the regulatory functions performed by activated astrocytes could represent an important pathogenic mechanism for neurodegenerative diseases. (c) 2005 Elsevier Inc. All rights reserved.