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星形胶质细胞的存在增强了海马细胞培养物中β淀粉样蛋白诱导的神经毒性。

The presence of astrocytes enhances beta amyloid-induced neurotoxicity in hippocampal cell cultures.

作者信息

Domenici M R, Paradisi S, Sacchetti B, Gaudi S, Balduzzi M, Bernardo A, Ajmone-Cat M A, Minghetti L, Malchiodi-Albedi F

机构信息

Laboratory of Pharmacology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.

出版信息

J Physiol Paris. 2002 Apr-Jun;96(3-4):313-6. doi: 10.1016/s0928-4257(02)00021-9.

Abstract

A characteristic feature of neuritic plaques in Alzheimer's disease is represented by the presence of activated astrocytes, surrounding dystrophic neurons and beta-amyloid deposition. To explore the role of astrocytes in in vitro beta-amyloid neurotoxicity, we studied the effect of beta-amyloid treatment in hippocampal neurons in two different cell models: pure cultures, where neurons were grown in absence of astrocytes and mixed cultures, where neurons were seeded on a confluent layer of astrocytes. We evaluated two characteristic aspects of in vitro beta-amyloid neurotoxicity: reduction of cell viability and degeneration of the neuritic tree. We demonstrated that neurons growing on astrocytes were more prone to the detrimental effect of the amyloid peptide, with respect to neurons grown in absence of the glial component. Our results support the hypothesis that beta-amyloid-astrocyte interaction can adversely condition neurons and contribute to neuronal damage in Alzheimer's disease.

摘要

阿尔茨海默病中神经炎性斑块的一个特征是存在活化的星形胶质细胞,其围绕着营养不良的神经元和β-淀粉样蛋白沉积。为了探究星形胶质细胞在体外β-淀粉样蛋白神经毒性中的作用,我们在两种不同的细胞模型中研究了β-淀粉样蛋白处理对海马神经元的影响:纯培养物,即神经元在无星形胶质细胞的情况下生长;混合培养物,即神经元接种在汇合的星形胶质细胞层上。我们评估了体外β-淀粉样蛋白神经毒性的两个特征方面:细胞活力降低和神经树突退化。我们证明,与在无胶质成分情况下生长的神经元相比,在星形胶质细胞上生长的神经元更容易受到淀粉样肽的有害影响。我们的结果支持这样的假设,即β-淀粉样蛋白与星形胶质细胞的相互作用会对神经元产生不利影响,并导致阿尔茨海默病中的神经元损伤。

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