von Bernhardi Rommy, Eugenín Jaime
Department of Neurology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O'Higgins 340, Santiago, Chile.
Brain Res. 2004 Oct 29;1025(1-2):186-93. doi: 10.1016/j.brainres.2004.07.084.
The brains of Alzheimer's disease (AD) patients present activated glial cells, amyloid plaques and dystrophic neurites. The core of amyloid plaques is composed of aggregated amyloid peptide (Abeta), a peptide known to activate glial cells and to have neurotoxic effects. We evaluated the capability of glial cells to mediate Abeta(1-42) cytotoxicity in hippocampal cultures. Conditioned media obtained from microglial cultures exposed to Abeta induced apoptosis of hippocampal cells. This pro-apoptotic effect was not observed in hippocampal cultures exposed to conditioned media obtained from mixed glial (astrocytes and microglia) cultures that had been exposed to Abeta. Microglia exposed to Abeta responded with reactive morphological changes, induction of iNOS, elevated nitric oxide production and decreased reductive metabolism. All these responses were attenuated by the presence of astrocytes. This astrocyte modulation was however, not observed when glial cells were exposed to proinflammatory factors (LPS+Interferon-gamma) alone or in combination with Abeta. Our results suggest that astrocytes and proinflammatory molecules are determining factors in the response of microglia to Abeta.
阿尔茨海默病（AD）患者的大脑存在活化的胶质细胞、淀粉样斑块和营养不良性神经突。淀粉样斑块的核心由聚集的淀粉样肽（Aβ）组成，该肽已知可激活胶质细胞并具有神经毒性作用。我们评估了胶质细胞在海马培养物中介导Aβ（1-42）细胞毒性的能力。从暴露于Aβ的小胶质细胞培养物中获得的条件培养基可诱导海马细胞凋亡。在暴露于已暴露于Aβ的混合胶质细胞（星形胶质细胞和小胶质细胞）培养物中获得的条件培养基的海马培养物中未观察到这种促凋亡作用。暴露于Aβ的小胶质细胞会出现反应性形态变化、诱导诱导型一氧化氮合酶（iNOS）、一氧化氮产生增加和还原代谢降低。星形胶质细胞的存在会减弱所有这些反应。然而，当胶质细胞单独或与Aβ联合暴露于促炎因子（脂多糖+干扰素-γ）时，未观察到这种星形胶质细胞调节作用。我们的结果表明，星形胶质细胞和促炎分子是小胶质细胞对Aβ反应的决定性因素。
