Salo P T, Tatton W G
Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada.
J Neurosci Res. 1993 Aug 15;35(6):664-77. doi: 10.1002/jnr.490350609.
Previous work in our laboratory revealed markedly different rates of age-related death of four monoaminergic neuronal populations in the C57BL/6 mouse. Although dorsal root ganglion neurons (DRGns) have been reported not to suffer similar age-related death in rodents, we determined if there is age-related death of the subpopulation of DRGns innervating the knee joints of C57BL/6 mice, which are known to develop degenerative arthritis with aging. The somata of dorsal root ganglion neurons innervating the mouse knee joint (KJ-DRGns) were identified by retrograde tracing with Fluoro-Gold (FG). Lumbar ganglia were serially sectioned and the numbers of FG-labelled KJ-DRGns counted at five ages encompassing the animal's life span. Changes in size of the total population of lumbar DRGns (L-DRGns) were estimated by counting nucleated somata from every fifth toluidine blue-stained serial section from the L3 and L4 lumbar ganglia at three different ages. Using a computer-assisted video morphometric technique somal areas were measured from random sections to determine the distribution of sizes of neurons in the KJ-DRGn and general lumbar DRGn populations at different ages. Counts of FG-labelled joint afferents were 238.5 +/- 80.3 (mean +/- SD) KJ-DRGns per knee at 2 months of age, declining to 103.2 +/- 20.1 by 24 months, representing a 57% loss over the average life span of the C57 mice. The loss occurred in two phases, with a rapid rate over the first 8 months of life and a more moderate rate of loss over the remaining months. L-DRGn numbers revealed a slower overall rate of loss in comparison to the KJ-DRGn population with an average 33.7% loss over the life span of this mouse. Somal size measurements revealed that the larger sizes of KJ-DRGns were lost over the first 8 months of life, with little change in the distribution of somal sizes thereafter. The distributions of sizes of the L-DRGn population did not change significantly over the life spans of the mice. The data provides evidence that the age-related loss of KJ-DRGns is significantly greater than DRGns in general, and may be particularly apparent in the population of larger sized presumed mechanoreceptor neurons. The loss of the KJ-DRGns is approximately reciprocal to the incidence rate of knee joint osteoarthritis reported for the C57BL/6 mice.
我们实验室之前的研究揭示了C57BL/6小鼠中四个单胺能神经元群体与年龄相关的死亡速率存在显著差异。尽管有报道称背根神经节神经元（DRGns）在啮齿动物中不会出现类似的与年龄相关的死亡，但我们研究了支配C57BL/6小鼠膝关节的DRGns亚群是否存在与年龄相关的死亡，已知C57BL/6小鼠随着年龄增长会发生退行性关节炎。通过用荧光金（FG）逆行追踪来识别支配小鼠膝关节的背根神经节神经元（KJ-DRGns）的胞体。对腰神经节进行连续切片，并统计五个年龄段（涵盖动物寿命）中FG标记的KJ-DRGns数量。通过对三个不同年龄段L3和L4腰神经节每隔五张甲苯胺蓝染色连续切片中的有核胞体进行计数，估算腰DRGns（L-DRGns）总数的变化。使用计算机辅助视频形态测量技术，从随机切片测量胞体面积，以确定不同年龄段KJ-DRGn和一般腰DRGn群体中神经元大小的分布。2个月龄时，每只膝关节FG标记的关节传入神经元计数为238.5±80.3（平均值±标准差）个KJ-DRGns，到24个月龄时降至103.2±20.1个，在C57小鼠的平均寿命期间损失了57%。损失分两个阶段发生，在生命的前8个月损失速率较快，在其余月份损失速率较为适中。与KJ-DRGn群体相比，L-DRGn数量的总体损失速率较慢，在该小鼠的寿命期间平均损失33.7%。胞体大小测量显示，较大尺寸的KJ-DRGns在生命的前8个月丢失，此后胞体大小分布变化不大。在小鼠的寿命期间，L-DRGn群体的大小分布没有显著变化。数据表明，与年龄相关的KJ-DRGns损失总体上显著大于DRGns，并且在较大尺寸的假定机械感受器神经元群体中可能尤为明显。KJ-DRGns的损失与报道的C57BL/6小鼠膝关节骨关节炎发病率大致呈反比。
