MYELIN

髓磷脂

• 批准号: 6233915
• 负责人: ALAN PETERS
• 金额: $ 18.89万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-01 至 1998-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6233915
• 关键词: Macaca mulatta; aging; axon; cognition; cognition disorders; electron microscopy; frontal lobe /cortex; hippocampus; magnetic resonance imaging; myelin; neural transmission; neuroanatomy; radioassay; retina; tritium; visual cortex; visual pathways

During the last grant period we examined several areas of the cerebral cortex of young (4 to 6 years of age) and old (over 25 years of age) rhesus monkeys and came to the conclusion that there is no significant loss of cortical neurons with age. However there are other significant changes both in the cortex and in the underlying white matter. The most obvious of these is a breakdown in the integrity of myelin. This is not demyelination in the sense that the axons are left bare, but a breakdown in the integrity of the sheats that might best be termed ~dysmyelination~. There is some evidence of axonal degeneration, but this is not pronounced in the cortex. Furthermore, in our study of the frontal cortex we found that there is a correlation between the extent of myelin breakdown and the performance of old monkeys on the delayed nonmatching to sample tasks. In addition, MCI scans of the cerebral hemispheres of our monkeys, show a loss of white matter, but not of gray matter, with age. And when the extent of loss of white matter is plotted against the behavioral performance of the monkeys, there is a significant correlation with the performance of the monkeys on the acquisition component of the delayed nonmatching to sample task. These results have lead us to believe that a breakdown in the integrity of myelin might underlie the cognitive deficits, since this would reduce the conduction rates along some axons and disrupt the timing of synaptic activity in neuronal circuits. Obviously, an in depth study of the effect of aging on myelin is important. We propose to continue MCI scans to obtain better data on the correlation between white matter loss and behavioral performance. In addition, we will use a new tritium quenching technique to determine whether myelin loss is more prevalent in some cortical areas that in others, and will correlate the results with the recorded behavior of the monkeys. Finally, we propose to examine the effect of aging on myelin sheaths by electron microscopy, to determine how sheaths break down, what size fibers are most affected, and whether the breakdown of the myelin occurs equally throughout the CNS, or whether it is more prominent in some fiber pathways than in others. For this purpose, we have chosen to examine the visual pathway, since this system offers a hierarchical system of fiber connections, as well as intracortical and extracortical connections, whose origins and terminations are well known.

在上一次资助期间，我们检查了大脑的几个区域 青年(4至6岁)和老年人(25岁以上)的皮质 和恒河猴得出的结论是，没有显著的 大脑皮层神经元随年龄增长而丧失。然而，还有其他 大脑皮层和脑白质的显著变化 物质。其中最明显的是 髓鞘。这不是脱髓鞘，因为轴突是 光秃秃的，但这可能会导致Sheats的诚信崩溃 最好将其称为~髓鞘障碍~。有一些轴突的证据 变性，但这在大脑皮层并不明显。此外， 在我们对额叶皮质的研究中，我们发现有一种 髓鞘破坏程度与运动成绩的相关性研究 对老猴子的延时不匹配，给样本任务。在……里面 此外，对我们猴子大脑半球的MCI扫描显示， 随着年龄的增长，脑白质会消失，但灰质不会消失。而当 白质丢失的程度与行为 在猴子的表现中，有显著的相关性 猴子在获取部分上的表现 延迟与样本任务不匹配。这些结果使我们得到了 相信髓鞘完整性的崩溃可能是 认知缺陷，因为这会降低传导率 一些轴突和扰乱神经元突触活动的时间 电路。 显然，对衰老对髓鞘影响的深入研究是 很重要。我们建议继续进行MCI扫描，以获得更好的数据 脑白质丢失与行为表现的相关性。 此外，我们将使用一种新的氚猝灭技术来 确定髓鞘丢失是否在某些皮质区更为普遍 并将结果与记录的结果相关联 猴子的行为。最后，我们建议研究一下 用电子显微镜观察髓鞘的老化情况 鞘的分解，什么大小的纤维受影响最大，以及 髓鞘的分解同样发生在整个中枢神经系统，或者 它是否在某些纤维通路中比在其他纤维通路中更为突出。 为此，我们选择研究视觉通路，因为 该系统还提供了光纤连接的分层系统 作为皮质内和皮质外的连接，其起源和 终止是众所周知的。