Paradisi Silvia, Sacchetti Benedetto, Balduzzi Maria, Gaudi Simona, Malchiodi-Albedi Fiorella
Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
Glia. 2004 May;46(3):252-60. doi: 10.1002/glia.20005.
In Alzheimer's disease brain, beta-amyloid (Abeta) deposition is accompanied by astrocyte activation, whose role in the pathogenesis of the disease is still unclear. To explore the subject, we compared Abeta neurotoxicity in pure hippocampal cultures and neuronal-astrocytic cocultures, where astrocytes conditioned neurons but were not in contact with them or Abeta. In the presence of astrocytes, neurons were protected from Abeta neurotoxicity. Neuritic dystrophy was reduced, synapses were partially preserved, and apoptosis was contrasted. The protection disappeared when astrocytes were also treated with Abeta, suggesting that Abeta-astrocyte interaction is deleterious for neurons. This was supported by comparing Abeta neurotoxicity in pure neurons and neurons grown on astrocytes. In this case, where astrocytes were also in contact with Abeta, neuritic damage was enhanced and expression of synaptic vesicle proteins decreased. Our results suggest that astrocytes can protect neurons from Abeta neurotoxicity, but when they interact with Abeta, the protection is undermined and neurotoxicity enhanced.
在阿尔茨海默病患者的大脑中，β-淀粉样蛋白（Aβ）沉积伴随着星形胶质细胞的激活，但其在该疾病发病机制中的作用仍不清楚。为了探究这一问题，我们比较了纯海马体培养物和神经元-星形胶质细胞共培养物中Aβ的神经毒性，在共培养物中，星形胶质细胞对神经元起到调节作用，但不与它们或Aβ接触。在有星形胶质细胞存在的情况下，神经元受到保护，免受Aβ神经毒性的影响。神经突营养不良减轻，突触部分得以保留，细胞凋亡受到抑制。当星形胶质细胞也用Aβ处理时，这种保护作用消失，这表明Aβ与星形胶质细胞的相互作用对神经元有害。通过比较纯神经元和在星形胶质细胞上生长的神经元中Aβ的神经毒性，这一点得到了证实。在这种情况下，星形胶质细胞也与Aβ接触，神经突损伤加剧，突触小泡蛋白的表达减少。我们的结果表明，星形胶质细胞可以保护神经元免受Aβ神经毒性的影响，但当它们与Aβ相互作用时，这种保护作用会被削弱，神经毒性会增强。
