Pizzi M, Valerio A, Ribola M, Spano P F, Memo M
Department of Biomedical Sciences and Biotechnologies, School of Medicine, University of Brescia, Italy.
Neuroreport. 1993 Jun;4(6):823-6. doi: 10.1097/00001756-199306000-00057.
Short-term exposure of primary cultures of cerebellar granule cells from neonatal rat brain to high concentrations of glutamate results in neuronal degeneration. We found that glutamate, before causing neuronal degeneration, induced a significant increase of Tau protein immunostaining. Time-course experiments revealed the increase ot Tau immunoreactivity to be maximal 2 h after the glutamate pulse. To investigate the possible role of newly synthesized Tau protein in the neurotoxic process activated by glutamate, cerebellar granule cells were preincubated with a specific Tau antisense oligonucleotide. This treatment resulted in (i) an inhibition of the glutamate-induced increase of Tau immunoreactivity and (ii) a decrease in the sensitivity of the neurones to neurotoxic concentrations of glutamate. These data indicate that new synthesis of the cytoskeleton-associated Tau protein is a crucial step in the cascade of events promoted by glutamate and leading to neurodegeneration.
新生大鼠脑小脑颗粒细胞原代培养物短期暴露于高浓度谷氨酸会导致神经元变性。我们发现，在导致神经元变性之前，谷氨酸会引起Tau蛋白免疫染色显著增加。时间进程实验显示，谷氨酸脉冲后2小时，Tau免疫反应性增加至最大。为了研究新合成的Tau蛋白在谷氨酸激活的神经毒性过程中的可能作用，小脑颗粒细胞用特异性Tau反义寡核苷酸进行预孵育。该处理导致：（i）抑制谷氨酸诱导的Tau免疫反应性增加；（ii）神经元对神经毒性浓度谷氨酸的敏感性降低。这些数据表明，细胞骨架相关Tau蛋白的新合成是谷氨酸促进并导致神经变性的一系列事件中的关键步骤。
