Examinando por Autor "Kotz, Catherine M."
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Ítem Effect of Housing Types on Growth, Feeding, Physical Activity, and Anxiety-Like Behavior in Male Sprague-Dawley Rats(Frontiers Media S.A., 2016-02) Teske, Jennifer A.; Perez-Leighton, Claudio Esteban; Noble, Emily E.; Wang, Chuanfeng; Billington, Charles J.; Kotz, Catherine M.Background: Animal welfare and accurate data collection are equally important in rodent research. Housing influences study outcomes and can challenge studies that monitor feeding, so housing choice needs to be evidence-based. The goal of these studies was to (1) compare established measures of well-being between rodents housed in wire grid-bottom floors with a resting platform compared to solid-bottom floors with bedding and (2) determine whether presence of a chewable device (Nylabone) affects orexin-A-induced hyperphagia. Methods: Rodents were crossed over to the alternate housing twice after 2-week periods. Time required to complete food intake measurements was recorded as an indicator of feasibility. Food intake stimulated by orexin-A was compared with and without the Nylabone. Blood corticosterone and hypothalamic BDNF were assessed. Results: Housing had no effect on growth, energy expenditure, corticosterone, hypothalamic BDNF, behavior, and anxiety measures. Food intake was disrupted after housing cross-over. Time required to complete food intake measurements was significantly higher for solid-bottom bedded cages. The Nylabone had no effect on orexin-A-stimulated feeding. Conclusion: Well-being is not significantly different between rodents housed on grid-bottom floors and those in solid-bottom-bedded cages based on overall growth and feeding but alternating between housing confounds measures of feeding. © Copyright © 2016 Teske, Perez-Leighton, Noble, Wang, Billington and Kotz.Ítem Orexin signaling in rostral lateral hypothalamus and nucleus accumbens shell in the control of spontaneous physical activity in high- and low-activity rats(American Physiological Society, 2017-03) Perez-Leighton, Claudio; Little, Morgan R.; Grace, Martha; Billington, Charles; Kotz, Catherine M.Spontaneous physical activity (SPA) describes activity outside of formal exercise and shows large interindividual variability. The hypothalamic orexin/hypocretin peptides are key regulators of SPA. Orexins drive SPA within multiple brain sites, including rostral lateral hypothalamus (LH) and nucleus accumbens shell (NAcSh). Rats with high basal SPA (high activity, HA) show higher orexin mRNA expression and SPA after injection of orexin-A in rostral LH compared with low-activity (LA) rats. Here, we explored the contribution of orexin signaling in rostral LH and NAcSh to the HA/LA phenotype. We found that HA rats have higher sensitivity to SPA after injection of orexin-A in rostral LH, but not in NAcSh. HA and LA rats showed similar levels of orexin receptor expression in rostral LH, and activation of orexin-producing neurons after orexin-A injection in rostral LH. Also, in HA and LA rats, the coinjection of orexin-A in rostral LH and NAcSh failed to further increase SPA beyond the effects of orexin-A in rostral LH. Pretreatment with muscimol, a GABAA receptor agonist, in NAcSh potentiated SPA produced by orexin-A injection in rostral LH in HA but not in LA rats. Our results suggest that a feedback loop from orexin-responsive neurons in rostral LH to orexin neurons and a the NAcSh-orexin neuron-rostral LH circuit regulate SPA. Overall, our data suggest that differences in orexin sensitivity in rostral LH and its modulation by GABA afferents from NAcSh contribute to individual SPA differences. © 2017 the American Physiological Society.Ítem Promotion of wakefulness and energy expenditure by orexin-a in the ventrolateral preoptic area(Associated Professional Sleep Societies,LLC, 2015-09) Mavanji, Vijayakumar; Perez-Leighton, Claudio E.; Kotz, Catherine M.; Billington, Charles J.; Parthasarathy, Sairam; Sinton, Christopher M.; Teske, Jennifer A.Study Objectives: The ventrolateral preoptic area (VLPO) and the orexin/hypocretin neuronal system are key regulators of sleep onset, transitions between vigilance states, and energy homeostasis. Reciprocal projections exist between the VLPO and orexin/hypocretin neurons. Although the importance of the VLPO to sleep regulation is clear, it is unknown whether VLPO neurons are involved in energy balance. The purpose of these studies was to determine if the VLPO is a site of action for orexin-A, and which orexin receptor subtype(s) would mediate these effects of orexin-A. We hypothesized that orexin-A in the VLPO modulates behaviors (sleep and wakefulness, feeding, spontaneous physical activity [SPA]) to increase energy expenditure. Design and Measurements: Sleep, wakefulness, SPA, feeding, and energy expenditure were determined after orexin-A microinjection in the VLPO of male Sprague-Dawley rats with unilateral cannulae targeting the VLPO. We also tested whether pretreatment with a dual orexin receptor antagonist (DORA, TCS-1102) or an OX2R antagonist (JNJ-10397049) blocked the effects of orexin-A on the sleep/wake cycle or SPA, respectively. Results: Orexin-A injected into the VLPO significantly increased wakefulness, SPA, and energy expenditure (SPA-induced and total) and reduced NREM sleep and REM sleep with no effect on food intake. Pretreatment with DORA blocked the increase in wakefulness and the reduction in NREM sleep elicited by orexin-A, and the OX2R antagonist reduced SPA stimulated by orexin-A. Conclusions: These data show the ventrolateral preoptic area is a site of action for orexin-A, which may promote negative energy balance by modulating sleep/wakefulness and stimulating spontaneous physical activity and energy expenditure.Ítem Role of spontaneous physical activity in prediction of susceptibility to activity based anorexia in male and female rats(Elsevier Inc., 2014-08) Perez-Leighton, Claudio E.; Grace, Martha; Grace, Martha; Kotz, Catherine M.Anorexia nervosa (AN) is a chronic eating disorder affecting females and males, defined by body weight loss, higher physical activity levels and restricted food intake. Currently, the commonalities and differences between genders in etiology of AN are not well understood. Animal models of AN, such as activity-based anorexia (ABA), can be helpful in identifying factors determining individual susceptibility to AN. In ABA, rodents are given an access to a running wheel while food restricted, resulting in paradoxical increased physical activity levels and weight loss. Recent studies suggest that different behavioral traits, including voluntary exercise, can predict individual weight loss in ABA. A higher inherent drive for movement may promote development and severity of AN, but this hypothesis remains untested. In rodents and humans, drive for movement is defined as spontaneous physical activity (SPA), which is time spent in low-intensity, non-volitional movements. In this paper, we show that a profile of body weight history and behavioral traits, including SPA, can predict individual weight loss caused by ABA in male and female rats with high accuracy. Analysis of the influence of SPA on ABA susceptibility in males and females rats suggests that either high or low levels of SPA increase the probability of high weight loss in ABA, but with larger effects in males compared to females. These results suggest that the same behavioral profile can identify individuals at-risk of AN for both male and female populations and that SPA has predictive value for susceptibility to AN.Ítem The orexin neuropeptide system: Physical activity and hypothalamic function throughout the aging process(Frontiers Media S.A., 2014) Zink, Anastasia N.; Perez-Leighton, Claudio Esteban; Kotz, Catherine M.There is a rising medical need for novel therapeutic targets of physical activity. Physical activity spans from spontaneous, low intensity movements to voluntary, high-intensity exercise. Regulation of spontaneous and voluntary movement is distributed over many brain areas and neural substrates, but the specific cellular and molecular mechanisms responsible for mediating overall activity levels are not well understood. The hypothalamus plays a central role in the control of physical activity, which is executed through coordination of multiple signaling systems, including the orexin neuropeptides. Orexin producing neurons integrate physiological and metabolic information to coordinate multiple behavioral states and modulate physical activity in response to the environment. This review is organized around three questions: (1) How do orexin peptides modulate physical activity? (2) What are the effects of aging and lifestyle choices on physical activity? (3) What are the effects of aging on hypothalamic function and the orexin peptides? Discussion of these questions will provide a summary of the current state of knowledge regarding hypothalamic orexin regulation of physical activity during aging and provide a platform on which to develop improved clinical outcomes in age-associated obesity and metabolic syndromes. © 2014 Zink, Perez-Leighton and Kotz.