Background: Spinal bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion mutation in the androgen receptor (AR) gene, and mutant AR is presumed to act in motoneurons to cause SBMA. However, we found that mice overexpressing wild-type (wt) AR solely in skeletal muscle fibers display the same androgen-dependent disease phenotype as when mutant AR is broadly expressed, challenging the assumptions that only an expanded AR can induce disease and that SBMA is strictly neurogenic. We have previously reported that AR toxicity was ligand dependent in our model, and that very few transgenic (tg) males survived beyond birth. Methods: We tested whether the AR antagonist flutamide could block perinatal toxicity. tg males were treated prenatally with flutamide and assessed for survival and motor behavior in adulthood. Results: Prenatal treatment with flutamide rescued tg male pups from perinatal death, and, as adults, such perinatally rescued tg males showed an SBMA phenotype that was comparable to that of previously described untreated tg males. Moreover, tg males carrying a mutant endogenous allele for AR – the testicular feminization mutation (tfm) – and thus having functional AR only in muscle fibers nevertheless displayed the same androgen-dependent disease phenotype as adults. Conclusions: These mice represent an excellent model to study the myogenic contribution to SBMA as they display many of the core features of disease as other mouse models. These data demonstrate that AR acting exclusively in muscle fibers is sufficient to induce SBMA symptoms and that flutamide is protective perinatally.
Spinal and bulbar muscular atrophy (SBMA) is a late-onset, progressive neurodegenerative disease linked to a polyglutamine (polyQ) expansion in the androgen receptor (AR). Men affected by SBMA show marked muscle weakness and atrophy, typically emerging midlife. Given the androgen-dependent nature of this disease, one might expect AR antagonists to have therapeutic value for treating SBMA. However, current work from animal models suggests otherwise, raising questions about whether polyQ-expanded AR exerts androgen-dependent toxicity through mechanisms distinct from normal AR function. In this study, we asked whether the nonsteroidal AR antagonist flutamide, delivered via a time-release pellet, could reverse or prevent androgen-dependent AR toxicity in three different mouse models of SBMA: the AR97Q transgenic (Tg) model, a knock-in (KI) model, and a myogenic Tg model. We find that flutamide protects mice from androgen-dependent AR toxicity in all three SBMA models, preventing or reversing motor dysfunction in the Tg models and significantly extending the life span in KI males. Given that flutamide effectively protects against androgen-dependent disease in three different mouse models of SBMA, our data are proof of principle that AR antagonists have therapeutic potential for treating SBMA in humans and support the notion that toxicity caused by polyQ-expanded AR uses at least some of the same mechanisms as normal AR before diverging to produce disease and muscle atrophy.
Foraging ecology and food patch studies are commonly used to elucidate the environmental perceptions of wild, free-ranging animals. Their application to captive animals, however, especially those in zoos, is still in its infancy. To illustrate some specific applications of zoo foraging ecology, we provide a study that evaluated: (i) whether patch use and giving-up densities (GUDs) can reveal areas of preference within an exhibit for zoo species; (ii) if food patches provide an effective form of behavioural enrichment; and (iii) if visitor interest and behaviour is affected by food patch presence. A combination of behavioural observations, and experimental food patches and giving-up densities were used to address these objectives in Parma wallabies (Macropus parma) and Patagonian cavies (Dolichotis patagonum) at Lincoln Park Zoo, Chicago, Illinois USA. GUDs revealed distinct areas of preference and aversion within the exhibit for cavies, but not so for the wallabies. For both species, presence of food patches increased foraging behaviours, decreased inactive behaviours, and increased within-exhibit movement, demonstrating that food patches serve as an effective behavioural enrichment technique. The use of food patches also revealed striking differences between individuals, particularly for the pair of cavies. There were encouraging trends toward increased visitor number and stay-time when food patches were present in each exhibit, but the effect was not statistically significant. These results suggest that utilising patch use, GUDs, and foraging theory in zoo populations may enhance animal welfare, and can inform improvements to exhibit design directly from the animal's perspective. We conclude with a broader discussion of zoo foraging ecology as an emerging field, with suggestions for future avenues of research.
Context There is growing recognition of the importance of animal personality in wildlife ecology and management. Individuals that differ consistently in their behaviours from others of the same population are considered to exhibit different personalities. Personality can be easily quantified with repeat tests on animals held in captivity. However, captive-based tests may not always be possible for logistical reasons and tests conducted in captivity can alter naturally occurring behaviours. Development of methods to assess personality in the field over short-term capture is an important alternative to long-term captive tests. Aims To develop and refine field-based tests that can be used to easily define personality traits of wild common brushtail possum (Trichosurus vulpecula), eliminating the need to bring individuals into captivity for an extended period of time. Methods We developed a series of short-term capture protocols to quantify personality traits of the common brushtail possum in the field, using handling-bag tests, modified open-field tests, trap-behaviour tests and release tests. Key results Personality traits of brushtail possums could be measured in several different ways, but refining methods was crucial to reveal traits efficiently. Behaviours related to several personality traits (boldness, docility and activity/exploration) could be measured rapidly in the field with our methods, and were repeatable over time. Conclusions Rapid, reliable and easy-to-perform quantification of personality of brushtail possums in the field is possible. This may sometimes be the only available option, and has advantages over long captive trials in terms of animal welfare and cost. Implications The present study provides a baseline for future research on the personality of common brushtail possums and its application to management and control strategies for the species.
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