Peters Alan
Department of Anatomy and Neurobiology, Boston University School of Medicine, 715, Albany Street, Boston, MA 02118, USA.
J Neurocytol. 2002 Sep-Nov;31(8-9):581-93. doi: 10.1023/a:1025731309829.
It was believed that the cause of the cognitive decline exhibited by human and non-human primates during normal aging was a loss of cortical neurons. It is now known that significant numbers of cortical neurons are not lost and other bases for the cognitive decline have been sought. One contributing factor may be changes in nerve fibers. With age some myelin sheaths exhibit degenerative changes, such as the formation of splits containing electron dense cytoplasm, and the formation on myelin balloons. It is suggested that such degenerative changes lead to cognitive decline because they cause changes in conduction velocity, resulting in a disruption of the normal timing in neuronal circuits. Yet as degeneration occurs, other changes, such as the formation of redundant myelin and increasing thickness suggest of sheaths, suggest some myelin formation is continuing during aging. Another indication of this is that oligodendrocytes increase in number with age. In addition to the myelin changes, stereological studies have shown a loss of nerve fibers from the white matter of the cerebral hemispheres of humans, while other studies have shown a loss of nerve fibers from the optic nerves and anterior commissure in monkeys. It is likely that such nerve fiber loss also contributes to cognitive decline, because of the consequent decrease in connections between neurons. Degeneration of myelin itself does not seem to result in microglial cells undertaking phagocytosis. These cells are probably only activated when large numbers of nerve fibers are lost, as can occur in the optic nerve.
人们曾认为，人类和非人类灵长类动物在正常衰老过程中出现认知衰退的原因是皮质神经元的丧失。现在已知，大量皮质神经元并未丧失，人们一直在寻找认知衰退的其他原因。一个促成因素可能是神经纤维的变化。随着年龄增长，一些髓鞘会出现退行性变化，比如形成含有电子致密细胞质的裂隙，以及形成髓鞘气球样结构。有人认为，这种退行性变化会导致认知衰退，因为它们会引起传导速度的改变，进而导致神经元回路正常时间节律的紊乱。然而，随着退变的发生，其他变化，比如多余髓鞘的形成以及髓鞘厚度的增加，表明衰老过程中仍有一些髓鞘在形成。这方面的另一个迹象是，少突胶质细胞数量会随着年龄增长而增加。除了髓鞘变化，体视学研究表明，人类大脑半球白质中的神经纤维有所减少，而其他研究则表明，猴子的视神经和前连合中的神经纤维也有减少。这种神经纤维的丧失很可能也会导致认知衰退，因为神经元之间的连接会因此减少。髓鞘本身的退变似乎并不会导致小胶质细胞进行吞噬作用。这些细胞可能只有在大量神经纤维丧失时才会被激活，比如在视神经中就会出现这种情况。
