Pérez-Capote Kamil, Serratosa Joan, Solà Carme
Department of Pharmacology and Toxicology, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Cientificas (CSIC), Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Glia. 2004 Feb;45(3):258-68. doi: 10.1002/glia.10329.
We studied the influence of glial cells on the neuronal response to glutamate toxicity in cerebellar granule cell cultures. We compared the effect of glutamate on neuronal viability in neuronal vs. neuronal-glial cultures and determined this effect after pretreating the cultures with the lipopolysaccharide (LPS) of Escherichia coli, agent widely used to induce glial activation. Morphological changes in glial cells and nitric oxide (NO) production were evaluated as indicators of glial activation. We observed that glutamate neurotoxicity in neuronal-glial cultures was attenuated in a certain range of glutamate concentration when compared to neuronal cultures, but it was enhanced at higher glutamate concentrations. This enhanced neurotoxicity was associated with morphological changes in astrocytes and microglial cells in the absence of NO production. LPS treatment induced morphological changes in glial cells in neuronal-glial cultures as well as NO production. These effects occurred in the absence of significant neuronal death. However, when LPS-pretreated cultures were treated with glutamate, the sensitivity of neuronal-glial cultures to glutamate neurotoxicity was increased. This was accompanied by additional morphological changes in glial cells in the absence of a further increase in NO production. These results suggest that quiescent glial cells protect neuronal cells from glutamate neurotoxicity, but reactive glial cells increase glutamate neurotoxicity. Therefore, glial cells play a key role in the neuronal response to a negative stimulus, suggesting that this response can be modified through an action on glial cells.
我们研究了神经胶质细胞对小脑颗粒细胞培养物中神经元对谷氨酸毒性反应的影响。我们比较了谷氨酸对神经元培养物与神经元-神经胶质细胞共培养物中神经元活力的影响，并在用大肠杆菌脂多糖（LPS，一种广泛用于诱导神经胶质细胞激活的物质）预处理培养物后测定了这种影响。评估神经胶质细胞的形态变化和一氧化氮（NO）生成作为神经胶质细胞激活的指标。我们观察到，与神经元培养物相比，在一定浓度范围内，神经元-神经胶质细胞共培养物中的谷氨酸神经毒性有所减弱，但在较高谷氨酸浓度下则增强。这种增强的神经毒性与星形胶质细胞和小胶质细胞的形态变化有关，且无NO生成。LPS处理可诱导神经元-神经胶质细胞共培养物中神经胶质细胞的形态变化以及NO生成。这些效应在无明显神经元死亡的情况下发生。然而，当用LPS预处理的培养物再用谷氨酸处理时，神经元-神经胶质细胞共培养物对谷氨酸神经毒性的敏感性增加。这伴随着神经胶质细胞的额外形态变化，且NO生成未进一步增加。这些结果表明，静止的神经胶质细胞可保护神经元细胞免受谷氨酸神经毒性，但反应性神经胶质细胞会增加谷氨酸神经毒性。因此，神经胶质细胞在神经元对负面刺激的反应中起关键作用，这表明这种反应可通过作用于神经胶质细胞来改变。
