Figure 1. Aged IL-10tm mice show reduced motor function and partial denervation of the neuromuscular junction.
(A) Isometric force versus in vivo stimulation frequency of the gastrocnemius muscle showed significantly reduced force in IL-10tm mice (aged control, n = 7; IL-10tm, n = 8). (B) Force normalized to gastrocnemius weight showed no difference in total force. (C) Total body and gastrocnemius weight are lower in IL-10tm mice as compared with those of age-matched control. (D and E) Kinetics of contraction assessed at 80 Hz showed the maximal rate of contraction (+dF/dt) was significantly lower in the IL-10tm mice (D), while the maximal rate of relaxation (–dF/dT) was unchanged (E). (F) Morphology of the neuromuscular junction (NMJ) was quantified with β-3 tubulin (green) to denote the presynaptic area and bungarotoxin (red) to visualize the postsynaptic area. Representative confocal image of an NMJ in old WT B6 mice (control) reveals the presynaptic neural structure (green) opposed to a prototypical postsynaptic NMJ end-plate. Adjacent is a representative NMJ from old IL-10tm mice showing the absence of presynaptic neural connectivity (green) and disorganized postsynaptic structure (red). (G) Semiquantitative analysis of NMJ morphology. The first panel shows the ratio of presynapatic to postsynapatic junctional area is significantly reduced in IL-10tm mice (P < 0.0001). The second panel shows the distribution of the ratio between control old B6 mice versus IL-10tm mice. (H and I) Cross section of whole gastrocnemius muscle with Wheat Germ Agglutinin (WGA) labeling to detect muscle fiber boundaries (fluorescence image inverted for clarity). (H) Muscle fibers from old control mice show rounded muscle fibers of variable size. Magnification, 10×. (I) Myofibers of IL-10tm mouse are smaller in diameter than control with many being angular in shape. (J) Quantification of muscle fiber cross sectional area (CSA) shows a significant (P < 0.0001) reduction in IL-10tm mice compared with age matched control.