The influence of spinal reflex arcs on lower limb movement cannot be understated, but the individual contribution of various parts of the reflex pathway, namely the primary motor cortex, spinal cord, and sciatic nerve, are incompletely known. This study aims to consider each of these to develop a better understanding of how spinal cord reflexes and the relationship between the central and peripheral nervous systems, particularly in terms of motor control. In the anesthetized rat, recording electrodes were placed in the tibialis anterior muscle of the hindlimb to record both the direct muscle response (M-wave) and the muscle reflex response (H-wave) in response to electrical stimulation of the sciatic nerve. After baseline recordings, thermal deactivation was used to selectively silence the primary motor cortex, spinal cord, or sciatic nerve in the rat and test the hypothesis that different locations exerted different effects on the excitability and timing of the spinal cord reflexes. Deactivation of motor cortex produced a faster or more excitable spinal cord reflex, whereas sciatic nerve deactivation produced a profound attenuation of both the M and the H waves. This study strongly supports the contention that the motor cortex, through pathways that travel through the spinal cord, normally serves to inhibit the excitability of spinal cord reflexes.

Merosin-deficient CMD type 1A (MDC1A) is the second most common form of congenital muscular dystrophy (CMD) that presents at or near birth. MDC1A is caused by a mutation in the LAMA2 gene which encodes a protein called laminin-2. The clinical manifestations of MDC1A include profound muscle weakness, muscle hypotonia, loss of independent ambulation, and respiratory failure. There is still no cure or effective treatment available for MDC1A patients. In this study we use the Lama2dyW (DyW) mouse model which shares analogous phenotypes with the MDC1A disease in humans. To this point, therapy development has mainly utilized single-mode therapy. While effective in attenuating some aspects of pathology, no single treatment has been able to completely ameliorate the multi-faceted pathology of laminin-2 deficiency. Therefore this study utilizes a combinatorial treatment strategy with Losartan and Growth Hormone to target multiple pathologies simultaneously. Losartan, an angiotensin II type 1 (AT1) receptor antagonist, is commonly used in hypertensive patients for its abilities to induce vasodilation. In the context of dystrophy, blocking AT1 receptor with losartan inhibits AT1-mediated TGF- signaling leading to decreased fibrosis, normalized muscle architecture, and improved muscle function and regeneration. Losartan does not, however, induce weight gain in models of muscular dystrophy. Growth hormone (GH) is well known to stimulate postnatal skeletal muscle growth as well as overall body weight mainly through Insulin-like Growth Factor 1 (IGF-1). IGF-1 induces muscle growth via Akt-mediated mTOR activation leading to increases in protein synthesis and consequent muscle fiber hypertrophy. Thus we hypothesize that the combination of Losartan and GH would alleviates chronic inflammation and fibrosis as well as induce weight/muscle gain in DyW mice. Dual treatment led to significant gains in total body weight as well as muscle function. In addition to the improvements of weights and activities, dual-treated mice showed a more normalized distribution of fiber size without increased total fiber number suggesting that dual treatment led to muscle hypertrophy not seen in untreated or Losartan-treated DyW mice. Myogenesis associated genes, and specifically late markers of myogenic differentiation were also significantly upregulated in dual-treated mice indicating a more complete and robust myogenic repair compared to untreated and Losartan-treated DyW mice, respectively. Dual treatment also led to increased expression of IGF-1 and IGF-1R as well as the glucose transporter glut4 suggesting that this strategy also affects insulin signaling. This study suggests that a combinatorial anti-fibrotic and pro-myogenic therapy achieves a more comprehensive amelioration of downstream pathologies greater than single-mode therapies and may be a more suitable treatment regimen for complex pathologies such as MDC1A.

In seeking answers to questions about how the human body functions under stressful situations, scientists, coaches, doctors, and athletes in general have all wondered about the role of exercise in the maintenance of good health. Good cardiovascular health, especially, is sought ardently, as it appears to be a major key to overall body fitness. Good cardiovascular health appears to go hand-in-hand with proper diet, proper rest, and proper exercise (1, 2). The exercise phenomenon has attracted much attention and poses many questions. Just what is occurring when a person or an animal gets "in shape" by exercising. What bodily changes are initiated during exercises which tax the body's metabolic machinery? To understand better the changes occurring with exercise, it would be of interest to examine and compare the metabolism of cardiac and skeletal muscles. Glycogen is considered a storage form of energy, as it is made up of glucose moieties, and it appears in all metabolizing mammalian cells (3). Yet because the level of glycogen remains at a fairly stable level in resting cells--reflecting a balance of synthesis and degradation of glycogen, any change in that level seen after a stressful situation, such as exercise, could be used as an indication of changes in cell metabolism associated with the stress (3). Thus, a change in the level of glycogen in either heart or skeletal muscle indicates a change in the utilization of energy-providing substrates, of which glycogen is one (A); an alteration in the concentration of the enzymes associated with glycogen synthesis or degradation (5, 6); or a change in some other regulatory mechanism associated with glycogenesis or glycogenolysis (7, 8). To clarify those changes occurring in the glycogen metabolism of heart and skeletal muscle, the changes can be monitored by measuring differences in glycogen levels in rats after various regimens of exercise and can be related to the conditions under which they happened (4, 9).

Excess adrenocorticosteroid hormones such as glucocorticoids and mineralocorticoids is well known to induce hypertension in several animal species as well as in humans. Therefore, the development of potent and specific glucocorticoid and mineralocorticoid antagonists with antihypertensive effects is clinically necessary. steroid hormone antagonists being used therapeutically present serious endocrinology side effects such as the widely used antimineralocorticoid, spironolactone. The antiglucocorticoids available so far have been active only in vitro or only weakly in viva. Recently, three new exciting adrenocorticosteroid hormone antagonists have been synthesized. RU 486 is a potent antiglucocorticoid (and antiprogesterone with potential as an abortifacient), RU 26752 and mespirenone, are novel mineralocorticoid antagonists. I studied the antihypertensive effect of RU 486, RU 26752 and mespirenone in Sprague- Dawley rats with dexamethasone- or aldosterone-induced hypertension. In addition, the effect of these antagonists on the hypertension developed by genetic model, spontaneously hypertensive rats (SHR) were also studied. The SHR is the closest animal model to human essential hypertension and it is believed that adrenocorticosteroid hormones are involved in the induction and maintenance of the hypertension. The results obtained from my studies showed that RU 486 administered simultaneously with dexamethasone prevented the hypertension induced by dexamethasone treatment. However, RU 486 had no effect on mineralocorticoid-induced hypertension. The administration of the antimineralocorticoid RU 26752 or mespirenone in combination with aldosterone successfully presented aldosterone-induced hypertension but not dexamethasone- induced hypertension. Surprisingly, RU 486 caused a significant increase in the blood pressure of the SHR whilst mespirenone caused a slight decrease in blood pressure as compared to control SHR. The effect of these antihormones on body/organ weights, fluid intake and urinary output was observed. Morphologically examination of the heart and kidney showed no abnormalities with treatment. These results suggest that 1) RU 486 is specific in preventing dexamethasone-induced hypertension; 2) RU 26752 and mespirenone are successful in preventing aldosterone-induced hypertension and 3) mineralocorticoids may be involved in the development and maintenance of hypertension in the SHR.

With differences in fetal growth patterns observed across racial demographics, interest in possible biological causes for these differences has increased. Prior works have studied the effects of insulin resistance in pregnancy on fetal fat deposition and growth in utero. One proposed mechanism to explain the physiological decrease in insulin sensitivity observed in normal pregnancy is the release of epigenetic factors such as placental miRNAs that have downstream effects on nutrient availability and fetal growth. The aim of this study was to identify placental miRNAs in women of different races and to establish expression patterns between these groups, specifically if expression patterns were related to measures of fetal growth and insulin resistance. Untargeted RNAseq and targeted RT-qPCR techniques were utilized for miRNA expression analysis and validation, respectively. Statistical modeling was used to interpret relationships between miRNA expression and maternal and neonatal body composition variables. qPCR results validated RNA sequencing data of differential miRNA expression between maternal racial groups. While miRNA-34c-5p and 192-5p fold changes were not correlated with maternal insulin resistance (as measured by HOMA-IR) in both non-Hispanic black and non-Hispanic white women, both miRNA-34c-5p and miRNA-192-5p were both positively correlated with neonatal body composition measures in neonates born to NHB women only. Further analysis of more miRNAs from additional RNAseq is planned. / 2022-06-08T00:00:00Z

The ability to supply cellular energy in the form of adenosine triphosphate (ATP) by oxidative phosphorylation is critical to maintaining muscle function and health. While conventional endurance exercise training has proven effective at increasing the maximal capacity for oxidative phosphorylation (Vmax ), it is not known whether exercise training stimulates mitochondrial ATP synthesis in resting muscle (Vrest). Recently, short-term high-intensity interval training (HIT) training has shown potent effects on Vmax. However, little is known about (1) the effects of short-term HIT on Vrest, and (2) the time course of adaptations in V rest and Vmax following short-term HIT. Healthy young males were recruited to participate in a 2-week training intervention (6 training sessions). Each session consisted of 4–6 bouts of 30-s sprints on a cycle ergometer. Phosphorus magnetic resonance spectroscopy was used to measure Vrest and Vmax in vivo in vastus lateralis: (i) prior to, (ii) 15 hours after a single session of exercise training, and (iii) after completing 6 sessions of exercise training. Two weeks of training increased peak whole-body oxygen consumption (35.8 ± 1.4 to 39.3 ± 1.6 ml·min−1·kg−1, p=0.01) and exercise capacity (217.0 ± 11.0 to 230.5 ± 11.7 W, p=0.04) on the cycle ergometer. While Vmax was unchanged after a single session of HIT, completion of six training sessions resulted in increased muscle oxidative capacity (p<0.004). In contrast, neither a single nor six training sessions altered Vrest (p=0.74). Metabolic flux through each pathway, during maximal voluntary contractions, remained unchanged after the first training session, but 6 training sessions increased the relative contribution of ATPOX (31 ± 2 vs. 39 ± 2 % of total ATP turnover, p<0.001), and lowered the relative contribution from ATP CK (49 ± 2 vs. 44 ± 1 %, p=0.004) and ATPGLY (20 ± 2 vs. 17 ± 1 %, p=0.03). This study provided novel information about the scope and timing of bioenergetic adaptations of skeletal muscle in young healthy men following high-intensity interval training. These results highlight the plasticity of skeletal muscle oxidative metabolism, which is critical for the design of future exercise training interventions for both clinical and healthy populations.

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BACKGROUND: Nutrient timing is an effective means of augmenting endurance exercise training and performance. Previous studies report that pre-exercise feeding can influence exercise metabolism up to 4 hours post-prandial. However, this timeline has been confirmed during waking hours only; little is known about how sleep within the post-prandial period may influence metabolism during subsequent exercise. This question is relevant to the endurance competitor, as race start-times often occur in early morning, limiting the opportunity for optimal feeding prior to competition without disrupting sleep or risking gastrointestinal distress. PURPOSE: To investigate the influence of a small, nutrient dense, pre-sleep chocolate milk (CM) beverage on morning metabolism and 10-km running performance in female athletes. METHODS: In a crossover design, twelve competitive female runners (age, 30 ± 7 yrs; VO2peak, 53 ± 4 ml·kg−1·min−1) ingested either pre-sleep CM or a non-nutritive, flavor-matched placebo (PL) ~30 min before sleep and 7-9 hrs before a morning performance running trial. Following initial appetite assessment (visual analogue scales) and resting metabolic rate (RMR), serum glucose (GLU) and lactate (LAC) measurements, the performance trial included a warm-up and three 5-min incremental loads at 55, 65, and 75% VO2peak (to measure respiratory exchange ratio (RER), GLU and LAC), followed by a 10-km treadmill time trial (TT). Paired t-tests, ±90% confidence intervals, and magnitude-based inferences were used to determine differences in means. Significance was accepted at P < 0.05. RESULTS: Relative to PL, CM showed a 'likely small decrease' in perceived hunger (P = 0.041, -22.3% mean effect), and a 'likely small increase' in RMR (P = 0.049, 4.8% mean effect), resting GLU (P = 0. 081, 3.7% mean effect), and RER at 55, 65, and 75% VO2peak (P = 0.115, 0.194, 0.164 and 2.1%, 1.6%, 1.4% mean effect, respectively). Exercise GLU revealed subtle, and unique trends following CM compared to PL. Specifically, GLU was 'possibly increased' during exercise at 65% VO2peak (P = 0.358, 2.0% mean effect) and 'likely trivially decreased' at 75% VO2peak (P = 0.561, -1.0% mean effect) following CM compared to PL. No differences in resting or exercise LAC, or 10-km TT performance (PL: 52.8 ± 8.4 mins versus CM: 52.8 ± 8.0 mins, P = 0.987, -0.1% mean effect, 'most likely trivial' decrement to performance following CM compared to PL) were noted between treatments. CONCLUSIONS: Nighttime supplementation of CM results in acute enhancement to morning metabolism via increased carbohydrate utilization during exercise, but has no apparent effects on 10-km running performance. These results suggest that the nighttime feeding timeline, specifically sleep imposed within the post-prandial period may extend tangible effects to metabolism to over 8 hours out from meal ingestion. / A Thesis submitted to the Department of Nutrition, Food and Exercise Sciences in partial fulfillment of the requirements for the degree of Master of Science. / Spring Semester, 2015. / March 16, 2015. / Exercise metabolism, Nighttime feeding, Performance, Post-prandial sleep, Pre-sleep nutrition / Includes bibliographical references. / Michael J. Ormsbee, Professor Directing Thesis; Lynn B. Panton, Committee Member; Robert J. Contreras, Committee Member.

There is clear evidence that obesity and asthma are among today’s most prevalent, threatening, and burdensome childhood afflictions. Research strongly suggests that these two disorders, when occurring concurrently, are in fact, a distinct disease state. There exists two prominent asthma phenotypes, both of which are related in different degrees with obesity. These are early-onset, atopic and late-onset, non-atopic obesity-related asthma. The linkage between obesity and asthma is complex as both disorders cause a variety of metabolic and immunological changes that can affect different, yet interconnecting compartments and functions of the body. The main objective of this review is to summarize the principal findings that pathologically link obesity and asthma and the pharmacologic and non-pharmacologic therapies that are currently in use to combat this disorder.

Bibliography: leaves 164-200. / This investigation examines certain aspects of the medial pontomedullary reticular formation (PMRF) microanatom y and neurotransmission and also the connections between the substantia nigra pars reticulata (SNr) and the PMRF in the rat. The anatomical distribution of the population of PMRF neurones was determined by combining physiological identification with electrical stimulation and retrograde HRP tract-tracing. A dual stimulating/deposition electrode was used to combine antidromic stimulation of PMRF cells with optimal retrograde labelling. 139 PMRF neurones were identified by means of their stereotaxic location and physiological criteria, namely; spontaneous discharge, polymodal sensory responses and large receptive fields.