Dietary composition regulates Drosophila mobility and cardiac physiology.

The impact of dietary composition on exercise capacity is a subject of intense study in both humans and model organisms. Interactions between diet and genetics are a crucial component of optimized dietary design. However, the genetic factors governing exercise response are still not well understood. The recent development of invertebrate models for endurance exercise is likely to facilitate study designs examining the conserved interactions between diet, exercise and genetics. As a first step, we used the Drosophila model to describe the effects of varying dietary composition on several physiological indices, including fatigue tolerance and climbing speed, cardiac performance, lipid storage and autophagy. We found that flies of two divergent genetic backgrounds optimize endurance and cardiac performance on relatively balanced low calorie diets. When flies are provided with unbalanced diets, diets higher in sugar than in yeast facilitate greater endurance at the expense of cardiac performance. Importantly, we found that dietary composition has a profound effect on various physiological indices, whereas total caloric intake per se has very little predictive value for performance. We also found that the effects of diet on endurance are completely reversible within 48 h if flies are switched to a different diet.

dFatp regulates nutrient distribution and long-term physiology in Drosophila.

Nutrient allocation and usage plays an important part in regulating the onset and progression of age-related functional declines. Here, we describe a heterozygous mutation in Drosophila (dFatp) that alters nutrient distribution and multiple aspects of physiology. dFatp mutants have increased lifespan and stress resistance, altered feeding behavior and fat storage, and increased mobility. Concurrently, mutants experience impairment of cardiac function. We show that endurance exercise reverses increased lipid storage in the myocardium and the deleterious cardiac function conferred by dFatp mutation. These findings establish a novel conserved genetic target for regulating lifespan and physiology in aging animals. These findings also highlight the importance of varying exercise conditions in assessing aging functions of model organisms.

The Drosophila PGC-1α homolog spargel modulates the physiological effects of endurance exercise.

Endurance exercise is an inexpensive intervention that is thought to provide substantial protection against several age-related pathologies, as well as inducing acute changes to endurance capacity and metabolism. Recently, it has been established that endurance exercise induces conserved alterations in physiological capacity in the invertebrate Drosophila model. If the genetic factors underlying these exercise-induced physiological alterations are widely conserved, then invertebrate genetic model systems will become a valuable tool for testing of genetic and pharmacological mimetics for endurance training. Here, we assess whether the Drosophila homolog of the vertebrate exercise response gene PGC-1α spargel (srl) is necessary or sufficient to induce exercise-dependent phenotypes. We find that reduction of srl expression levels acutely compromises negative geotaxis ability and reduces exercise-induced improvement in both negative geotaxis and time to exhaustion. Conversely, muscle/heart specific srl overexpression improves negative geotaxis and cardiac performance in unexercised flies. In addition, we find that srl overexpression mimics some, but not all, exercise-induced phenotypes, suggesting that other factors also act in parallel to srl to regulate exercise-induced physiological changes in muscle and heart.

Quantitative comparison of myocardial fiber structure between mice, rabbit, and sheep using diffusion tensor cardiovascular magnetic resonance.

BACKGROUND: Accurate interpretations of cardiac functions require precise structural models of the myocardium, but the latter is not available always and for all species. Although scaling or substitution of myocardial fiber information from alternate species has been used in cardiac functional modeling, the validity of such practice has not been tested. METHODS: Fixed mouse (n = 10), rabbit (n = 6), and sheep (n = 5) hearts underwent diffusion tensor imaging (DTI). The myocardial structures in terms of the left ventricular fiber orientation helix angle index were quantitatively compared between the mouse rabbit and sheep hearts. RESULTS: The results show that significant fiber structural differences exist between any two of the three species. Specifically, the subepicardial fiber orientation, and the transmural range and linearity of fiber helix angles are significantly different between the mouse and either rabbit or sheep. Additionally, a significant difference was found between the transmural helix angle range between the rabbit and sheep. Across different circumferential regions of the heart, the fiber orientation was not found to be significantly different. CONCLUSIONS: The current study indicates that myocardial structural differences exist between different size hearts. An immediate implication of the present findings for myocardial structural or functional modeling studies is that caution must be exercised when extrapolating myocardial structures from one species to another.

Reliability of fMRI motor tasks in structures of the corticostriatal circuitry: implications for future studies and circuit function.

The corticostriatal circuits are important information processing networks. There is evidence that these circuits may be dysfunctional in a variety of neuropsychiatric conditions ranging from Parkinson's disease to bipolar disorder. Cross-sectional fMRI studies may clarify normal circuit function, and longitudinal studies may provide information on changes related to age in control subjects, as well as illness progression and treatment response in patient groups. In this paper, we report a comprehensive analysis of the utility of several motor tasks as cross-sectional and longitudinal probes of corticostriatal function in terms of their activation strength and reliability. Our findings suggest that the motor tasks studied can be useful probes of corticostriatal function for studies utilizing group comparisons. However, longitudinal clinical studies in which individual results are important will need to take into account wide variation in individual activation and reliability. For example, measures of activation strength and reliability based on percent signal change display a dichotomy between simple motor tasks, which have high reliability and low activation, and complex tasks, which have lower reliability and higher activation. Size and overlap ratios calculated from activation maps produced a different view of reliability than intraclass correlation coefficients (ICC) based on percent signal change. Finally, these results suggest that the corticostriatal circuitry exhibit individualized responses to motor adaptation.

An fMRI motor activation paradigm demonstrates abnormalities of putamen activation in females with panic disorder.

BACKGROUND: The neurobiology of panic disorder is incompletely understood. The aim of this study was to determine if functional abnormalities of the putamen occur in panic disorder. METHODS: Activation patterns of 12 female subjects with panic disorder were compared to 18 female healthy controls using functional MRI at 3 T. A motor activation paradigm was used to probe putamen function. RESULTS: A complex motor activation paradigm for the non-dominant hand revealed decreased activation of the bilateral putamen among subjects with panic disorder. LIMITATIONS: The sample size was a relatively small cohort of non-depressed females. Further, some panic disorder subjects were taking medications and/or had comorbid conditions. However, second-level regression analyses did not reveal any correlations between medication use or comorbidity and activation patterns demonstrated by the non-dominant hand complex task. Finally, we used a post-hoc approach to determine the magnitude of global fMRI signal as a surrogate index of the global cerebral blood flow as a means of controlling for possible confounds from reduction of BOLD signal secondary to cerebral vasoconstriction resulting from possible hyperventilation among panic subjects. A more compelling approach would have been to record the respiratory data from subjects during scanning. CONCLUSIONS: Our findings suggest that putamen dysfunction occurs in at least some cases of panic disorder. We also provide preliminary evidence that a complex motor task for the non-dominant hand is a useful probe of putamen function in this disorder.

Virtual histology of transgenic mouse embryos for high-throughput phenotyping.

A bold new effort to disrupt every gene in the mouse genome necessitates systematic, interdisciplinary approaches to analyzing patterning defects in the mouse embryo. We present a novel, rapid, and inexpensive method for obtaining high-resolution virtual histology for phenotypic assessment of mouse embryos. Using osmium tetroxide to differentially stain tissues followed by volumetric X-ray computed tomography to image whole embryos, isometric resolutions of 27 mum or 8 mum were achieved with scan times of 2 h or 12 h, respectively, using mid-gestation E9.5-E12.5 embryos. The datasets generated by this method are immediately amenable to state-of-the-art computational methods of organ patterning analysis. This technique to assess embryo anatomy represents a significant improvement in resolution, time, and expense for the quantitative, three-dimensional analysis of developmental patterning defects attributed to genetically engineered mutations and chemically induced embryotoxicity.