Morphometry and oxidative capacity of slow-twitch (type I) and fast-twitch (type IIa and IIb) muscle fibers obtained from vastus lateralis needle biopsies were compared between younger (21-30 yr) and older (51-62 yr) normal fit (maximal O2 uptake = 47.0 vs. 32.3 ml.kg-1.min-1) and endurance-trained (66.3 vs. 52.7 ml.kg-1.min-1) men (n = 6/group). The older groups had smaller type IIa (31%) and IIb (40%) fiber areas and fewer capillaries surrounding these fibers than did younger groups. The reduced type II fiber areas and capillary contacts associated with aging were also observed in the older trained men. However, the capillary supply per unit type II fiber area was not affected by age but was enhanced by training. Additionally, on the basis of quantitative histochemical analysis, succinate dehydrogenase activities of type IIa fibers in the older trained men [4.07 +/- 0.68 (SD) mmol.min-1.l-1] were similar to those observed in younger trained men (4.00 +/- 0.48 mmol.min-1.l-1) and twofold higher than in older normal fit men (2.01 +/- 0.65 mmol.min-1.l-1; age x fitness interaction, P < 0.05). Type I muscle fibers were unaffected by age but were larger and had more capillary contacts and higher succinate dehydrogenase activities in the trained groups. The findings of this study suggest that aging results in a decrease in type II fiber size and oxidative capacity in healthy men and that this latter effect can be prevented by endurance training. Conclusions regarding the effects of age and training status on muscle capillarization depend largely on how these data are expressed.

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We reported previously that mice lacking one brain-derived neurotrophic factor (BDNF) allele demonstrate elevated striatal dopamine (DA) concentrations but impaired behavioral responses involving the nigrostriatal dopaminergic (NSDA) system. To test the hypothesis that these elevated striatal DA concentrations are associated with perturbed NSDA functioning, we compared striatal DA output between heterozygous mutant (+/-) and wild-type littermate control (+/+) BDNF mice under conditions of an intact NSDA system, as well as following methamphetamine (MA)-induced neurotoxicity. Basal DA output from superfused CS tissue fragments did not differ between +/+ and +/- BDNF mice. Potassium (K+) stimulated DA outputs from intact striatal fragments of +/+ mice were significantly greater than that of +/- BDNF mice. Following MA treatment, K+ stimulated DA output of +/+ mice was statistically equivalent to +/- BDNF mice. Striatal DA concentrations of +/- BDNF mice were elevated, albeit not significantly, in both intact and MA-treated mice relative to +/+ mice. Following MA treatment, striatal DA concentrations were significantly decreased for both genotypes; however, the degree of DA depletion was significantly greater in +/+ mice. Analyzed collectively, these data show the differential effects exerted by a BDNF mutation upon striatal DA concentrations and output. Notably, lower striatal DA concentrations of +/+ vs. +/- BDNF mice can be contrasted with the significantly greater K+ stimulated DA output from the former. This difference was abolished following MA treatment. These results suggest that processes involved with the dynamics of DA release within the NSDA system may be compromised in +/- BDNF mutant mice.

The soleus muscles of fetal rats were examined by electron microscopy to determine whether the early differentiation of muscle spindles is dependent upon sensory innervation, motor innervation, or both. Simple unencapsulated afferent-muscle contacts were observed on the primary myotubes at 17 and 18 days of gestation. Spindles, encapsulations of muscle fibers innervated by afferents, could be recognized early on day 18 of gestation. The full complement of spindles in the soleus muscle was present at day 19, in the region of the neuromuscular hilum. More afferents innervated spindles at days 18 and 19 of gestation than at subsequent developmental stages, or in adult rats; hence, competition for available myotubes may exist among afferents early in development. Some of the myotubes that gave rise to the first intrafusal (bag2) fiber had been innervated by skeletomotor (alpha) axons prior to their incorporation into spindles. However, encapsulated intrafusal fibers received no motor innervation until fusimotor (gamma) axons innervated spindles 3 days after the arrival of afferents and formation of spindles, at day 20. The second (bag1) intrafusal fiber was already formed when gamma axons arrived. Thus, the assembly of bag1 and bag2 intrafusal fibers occurs in the presence of sensory but not gamma motor innervation. However, transient innervation of future bag2 fibers by alpha axons suggests that both sensory and alpha motor neurons may influence the initial stages of bag2 fiber assembly. The confinement of nascent spindles to a localized region of the developing muscle and the limited number of spindles in developing muscles in spite of an abundance of afferents raise the possibility that afferents interact with a special population of undifferentiated myotubes to form intrafusal fibers.