Successive bouts of cycling stimulates genes associated with mitochondrial biogenesis.

Exercise increases mRNA for genes involved in mitochondrial biogenesis and oxidative enzyme capacity. However, little is known about how these genes respond to consecutive bouts of prolonged exercise. We examined the effects of 3 h of intensive cycling performed on three consecutive days on the mRNA associated with mitochondrial biogenesis in trained human subjects. Forty trained cyclists were tested for VO(2max) (54.7 +/- 1.1 ml kg(-1) min(-1)). The subjects cycled at 57% watts(max) for 3 h using their own bicycles on CompuTrainer Pro Model trainers (RacerMate, Seattle, WA) on three consecutive days. Muscle biopsies were obtained from the vastus lateralis pre- and post-exercise on days one and three. Muscle samples were analyzed for mRNA content of peroxisome proliferator receptor gamma coactivator-1 alpha (PGC-1alpha), sirtuin 1 (Sirt-1), cytochrome c, and citrate synthase. Data were analyzed using a 2 (time) x 2 (day) repeated measures ANOVA. Of the mRNA analyzed, the following increased from pre to post 3 h rides: cytochrome c (P = 0.006), citrate synthase (P = 0.03), PGC-1alpha (P < 0.001), and Sirt-1 (P = 0.005). The following mRNA showed significant effects from days one to three: cytochrome c (P < 0.001) and citrate synthase (P = 0.01). These data show that exhaustive cycling performed on three consecutive days resulted in both acute and chronic stimuli for mRNA associated with mitochondrial biogenesis in already trained subjects. This is the first study to illustrate an increase in sirtuin-1 mRNA with acute and chronic exercise. These data contribute to the understanding of mRNA expression during both acute and successive bouts of prolonged exercise.

Activity level, apoptosis, and development of cachexia in Apc(Min/+) mice.

Criteria for diagnosing cachexia in adults include unintentional loss in body weight, decreased strength, fatigue, anorexia, and low muscle mass. Cachexia is also associated with systemic inflammation, altered metabolism, and anemia. The Apc(Min/+) mouse is a model of cachexia directly related to intestinal tumor burden and subsequent chronic inflammation. These mice also demonstrate muscle weakness, fatigue, decreased volitional activity, and elevated circulating IL-6 levels. The purpose of this study was to determine the time course of changes in physical activity and their relationship to anemia, muscle apoptosis, and muscle mass and body mass loss during cachexia. A subset of male Apc(Min/+) mice were given access to voluntary activity wheels from 5 to 26 wk of age, while sedentary male Apc(Min/+) mice were housed in cages lacking wheels. At the study's end mice were stratified by cachectic symptoms. Severely cachectic mice had decreased wheel running performance at 15 wk of age, while anemia and body weight loss were not present until 18 wk of age. Severely cachectic mice had lower hemoglobin levels compared with mildly cachectic mice at 13, 18, and 22 wk of age. Severely cachectic mice also demonstrated threefold more BCL2-associated X protein (BAX) protein in the gastrocnemius muscle at 26 wk of age compared with mildly cachectic mice. In sedentary Apc(Min/+) mice at 26 wk of age anemia was present, and markers of apoptosis were induced in severely cachectic muscle. Proapoptotic protein expression was induced in both red and white portions of gastrocnemius muscle as well as in soleus muscle of severely cachectic mice compared with mildly cachectic mice. These data demonstrate that decrements in wheel running performance precede loss of body mass and that inherent muscle oxidative capacity is not protective against muscle apoptosis.

Trail making test errors and executive function in schizophrenia and depression.

The Trail Making Test (TMT) frequently is used as a measure of executive cognitive function. However, traditional use of test completion time as the primary outcome score does not give the more detailed information on cognitive processes that analysis of test-taking errors may provide. The present study compared TMT performance of three groups: patients with schizophrenia, patients with major depression, and healthy control participants (n = 30 for each group). Three operationally defined error types were examined: (a) tracking, (b) perseverative, and (c) proximity. Although both patient groups were slower than the healthy control group, only the schizophrenia group made significantly more errors, particularly tracking errors, suggesting a greater degree of cognitive disorganization. Within-group analysis of a larger group of schizophrenia patients (n = 84) revealed that TMT time was most strongly associated with the Withdrawal-Retardation factor of the Brief Psychiatric Rating scale. In contrast, TMT errors were most strongly associated with the Conceptual Disorganization factor. Comparisons of TMT scores and other cognitive tests showed moderate to high associations with tests of working memory, psychomotor speed, and executive function. Stepwise regression analysis revealed an independent association between Digit Cancellation and Part B Time, indicating a unique contribution of visuomotor scanning to performance. In contrast, Part B errors were uniquely associated with the Verbal Series Attention Test and the Token Test, tests of mental tracking and executive-mediated working memory, respectively. These findings demonstrate the utility of TMT error analysis in revealing cognitive deficits not traditionally captured using completion time as the sole outcome variable.