Sternfeld M, Shoham S, Klein O, Flores-Flores C, Evron T, Idelson G H, Kitsberg D, Patrick J W, Soreq H
The Eric Roland Center for Neurodegenerative Diseases, Department of Biological Chemistry, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8647-52. doi: 10.1073/pnas.140004597.
Acute stress increases the risk for neurodegeneration, but the molecular signals regulating the shift from transient stress responses to progressive disease are not yet known. The "read-through" variant of acetylcholinesterase (AChE-R) accumulates in the mammalian brain under acute stress. Therefore, markers of neurodeterioration were examined in transgenic mice overexpressing either AChE-R or the "synaptic" AChE variant, AChE-S. Several observations demonstrate that excess AChE-R attenuates, whereas AChE-S intensifies, neurodeterioration. In the somatosensory cortex, AChE-S transgenics, but not AChE-R or control FVB/N mice, displayed a high density of curled neuronal processes indicative of hyperexcitation. In the hippocampus, AChE-S and control mice, but not AChE-R transgenics, presented progressive accumulation of clustered, heat shock protein 70-immunopositive neuronal fragments and displayed a high incidence of reactive astrocytes. Our findings suggest that AChE-R serves as a modulator that may play a role in preventing the shift from transient, acute stress to progressive neurological disease.
急性应激会增加神经退行性变的风险，但调节从短暂应激反应向进行性疾病转变的分子信号尚不清楚。乙酰胆碱酯酶（AChE-R）的“通读”变体在急性应激下会在哺乳动物大脑中积累。因此，在过表达AChE-R或“突触”AChE变体AChE-S的转基因小鼠中检测了神经退化的标志物。多项观察结果表明，过量的AChE-R会减弱神经退化，而AChE-S会加剧神经退化。在躯体感觉皮层中，AChE-S转基因小鼠（而非AChE-R或对照FVB/N小鼠）表现出高密度的卷曲神经元突起，提示存在过度兴奋。在海马体中，AChE-S和对照小鼠（而非AChE-R转基因小鼠）出现了聚集的、热休克蛋白70免疫阳性神经元碎片的逐渐积累，并显示出反应性星形胶质细胞的高发生率。我们的研究结果表明，AChE-R作为一种调节因子，可能在防止从短暂的急性应激向进行性神经疾病的转变中发挥作用。
