Carpenter M K, Crutcher K A, Kater S B
Department of Anatomy and Neurobiology, Colorado State University, Fort Collins 80523.
Neurobiol Aging. 1993 May-Jun;14(3):207-15. doi: 10.1016/0197-4580(93)90002-s.
Although senile plaques represent a consistent neuropathological feature in Alzheimer's brains, it is not known what role plaques play in the etiology of the disease. Both growth-promoting and growth-inhibiting influences have been postulated. One of the major components in plaques, beta-amyloid, has been shown to affect neuron survival and neurite outgrowth in vitro. Because plaques consist of other components in addition to beta-amyloid, we undertook the present study to determine whether neuronal survival and neurite outgrowth are affected by the presence of a senile plaque. This was accomplished by using cryostat sections from the cerebral cortex of Alzheimer's patients as a substratum for cultured rat hippocampal neurons. Evaluation of these living neurons on Alzheimer's tissue demonstrated that senile plaques affect the amount, complexity, and direction of neurite outgrowth. In addition, neurons were more likely to extend processes away from plaques rather than toward a plaque. Although cell survival on plaques and in control regions was similar, cell survival was significantly reduced in the peri-plaque region. These observations suggest that senile plaques could have deleterious effects on neural organization in situ.
尽管老年斑是阿尔茨海默病大脑中一种持续存在的神经病理学特征，但尚不清楚斑块在该疾病的病因中起什么作用。促进生长和抑制生长的影响都已被推测。斑块的主要成分之一β-淀粉样蛋白已被证明在体外会影响神经元存活和神经突生长。由于斑块除了β-淀粉样蛋白外还由其他成分组成，我们进行了本研究，以确定老年斑的存在是否会影响神经元存活和神经突生长。这是通过使用来自阿尔茨海默病患者大脑皮层的冷冻切片作为培养大鼠海马神经元的基质来实现的。对这些在阿尔茨海默病组织上的活神经元进行评估表明，老年斑会影响神经突生长的数量、复杂性和方向。此外，神经元更有可能从斑块处向外延伸突起，而不是朝向斑块延伸。尽管斑块上和对照区域的细胞存活率相似，但斑块周围区域的细胞存活率显著降低。这些观察结果表明，老年斑可能对原位神经组织产生有害影响。
