Age-related loss of knee joint afferents in mice

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.