Ivins K J, Bui E T, Cotman C W
Institute for Brain Aging and Dementia, University of California at Irvine, 92697, USA.
Neurobiol Dis. 1998 Nov;5(5):365-78. doi: 10.1006/nbdi.1998.0228.
Many apoptotic insults, including beta-amyloid, cause neuritic degeneration. The possibility that apoptotic insults act directly on neurites was investigated in experiments using compartmented cultures of hippocampal neurons. Neurites in modified Campenot chambers displayed morphological signs of degeneration, including beading or blebbing, when exposed to beta-amyloid. At short time points neurite degeneration was limited to the distal portions of neurites directly exposed to beta-amyloid. Furthermore, annexin V binding detected extracellular exposure of phosphatidylserine in portions of neurites directly exposed to apoptotic insults. Pretreatment of the cultures with zVAD-fmk blocked annexin V binding induced by beta-amyloid and concanavalin A, suggesting that caspase activity was required. Caspase activation was also visualized in neurites locally exposed to apoptotic insults. Together these results show that apoptotic insults cause local neurite degeneration which displays morphological and biochemical characteristics of apoptosis and suggest that neurite degeneration may use mechanisms common to apoptosis.
许多凋亡刺激因素，包括β-淀粉样蛋白，都会导致神经突退变。在使用海马神经元分隔培养物的实验中，研究了凋亡刺激因素直接作用于神经突的可能性。当暴露于β-淀粉样蛋白时，改良坎佩诺特培养室中的神经突呈现出退变的形态学迹象，包括串珠样或起泡。在短时间点，神经突退变仅限于直接暴露于β-淀粉样蛋白的神经突远端部分。此外，膜联蛋白V结合检测到直接暴露于凋亡刺激因素的神经突部分出现磷脂酰丝氨酸的细胞外暴露。用zVAD-fmk预处理培养物可阻断β-淀粉样蛋白和伴刀豆球蛋白A诱导的膜联蛋白V结合，表明半胱天冬酶活性是必需的。在局部暴露于凋亡刺激因素的神经突中也观察到了半胱天冬酶激活。这些结果共同表明，凋亡刺激因素会导致局部神经突退变，表现出凋亡的形态学和生化特征，并提示神经突退变可能利用了凋亡的共同机制。
