Sloane J A, Hollander W, Moss M B, Rosene D L, Abraham C R
Department of Pathology, Boston University School of Medicine, MA 02118, USA.
Neurobiol Aging. 1999 Jul-Aug;20(4):395-405. doi: 10.1016/s0197-4580(99)00066-4.
Activated microglia are important pathological features of a variety of neurological diseases, including the normal aging process of the brain. Here, we quantified the level of microglial activation in the aging rhesus monkey using antibodies to HLA-DR and inducible nitric oxide synthase (iNOS). We observed that 3 out of 5 white matter areas but only 1 of 4 cortical gray matter regions examined showed significant increases in two measures of activated microglia with age, indicating that diffuse white matter microglial activation without significant gray matter involvement occurs with age. Substantial levels of iNOS and 3-nitrotyrosine, a marker for peroxynitrite, increased diffusely throughout subcortical white matter with age, suggesting a potential role of nitric oxide in age-related white matter injury. In addition, we found that the density of activated microglia in the subcortical white matter of the cingulate gyrus and the corpus callosum was significantly elevated with cognitive impairment in elderly monkeys. This study suggests that microglial activation increases in white matter with age and that these increases may reflect the role of activated microglia in the general pathogenesis of normal brain aging.
活化的小胶质细胞是包括大脑正常衰老过程在内的多种神经疾病的重要病理特征。在此，我们使用针对人类白细胞抗原-DR（HLA-DR）和诱导型一氧化氮合酶（iNOS）的抗体，对衰老恒河猴的小胶质细胞活化水平进行了量化。我们观察到，在检查的5个白质区域中有3个区域，但4个皮质灰质区域中只有1个区域显示，随着年龄增长，活化小胶质细胞的两项指标显著增加，这表明随着年龄增长，会出现无明显灰质受累的弥漫性白质小胶质细胞活化。随着年龄增长，iNOS和过氧亚硝酸盐标志物3-硝基酪氨酸的大量水平在整个皮质下白质中弥漫性增加，提示一氧化氮在与年龄相关的白质损伤中可能发挥作用。此外，我们发现，老年猴子出现认知障碍时，扣带回和胼胝体皮质下白质中活化小胶质细胞的密度显著升高。这项研究表明，随着年龄增长，白质中的小胶质细胞活化增加，并且这些增加可能反映了活化小胶质细胞在正常脑衰老一般发病机制中的作用。
