Atlantic Salmon Reovirus Infection Causes a CD8 T Cell Myocarditis in Atlantic Salmon (Salmo salar L.)

Heart and skeletal inflammation (HSMI) of farmed Atlantic salmon (Salmo salar L.) is a disease characterized by a chronic myocarditis involving the epicardium and the compact and spongious part of the heart ventricle. Chronic myositis of the red skeletal muscle is also a typical finding of HSMI. Piscine reovirus (PRV) has been detected by real-time PCR from farmed and wild salmon with and without typical changes of HSMI and thus the causal relationship between presence of virus and the disease has not been fully determined [1]. In this study we show that the Atlantic salmon reovirus (ASRV), identical to PRV, can be passaged in GF-1 cells and experimental challenge of naïve Atlantic salmon with cell culture passaged reovirus results in cardiac and skeletal muscle pathology typical of HSMI with onset of pathology from 6 weeks, peaking by 9 weeks post challenge. ASRV replicates in heart tissue and the peak level of virus replication coincides with peak of heart lesions. We further demonstrate mRNA transcript assessment and in situ characterization that challenged fish develop a CD8+ T cell myocarditis

Sex-specific development of spatial orientation is independent of peripubertal gonadal steroids

Prenatal exposure to androgens has been shown to modulate brain development, resulting in changed behavioral attitudes, sexual orientation and cognitive functions, including processing of spatial information. Whether later changes in gonadotropic hormones during puberty induce further organizational effects within the brain is still insufficiently understood. The purpose of this study was to assess development of spatial orientation before and after the time of normal pubertal development, in an ovine model where half of the animals did not undergo typical reproductive maturation due to the pharmacological blockade of gonadotropin releasing hormone receptor (GnRHR) signaling. The study formed part of a larger trial and utilized 46 pairs of same sex Scottish Mule Texel Cross twins (22 female and 24 male). One twin remained untreated throughout (control) while the other received a subcutaneous GnRH agonist (GnRHa: Goserelin-Acetate) implant every fourth week. GnRHa treatment began at eight and 28 weeks of age, in males and females respectively, because the timing of the pubertal transition is sexually differentiated in sheep as it is in humans. Spatial orientation was assessed at three different time points: eight weeks of age, before puberty and treatment in both sexes; 28 weeks of age, after 20 weeks GnRHa treatment in males and before puberty and GnRHa treatment in females; and at 48 weeks of age, which is after the normal time of the pubertal transition in both sexes. Spatial orientation was tested in a spatial maze with traverse time as the main outcome measure. GnRHa treatment did not affect spatial maze performance as no significant differences in traverse time between treated and untreated animals were observed at any time-point. Adolescent females (48 weeks of age) traversed the maze significantly faster than adolescent males, whereas no sex differences in traverse time were seen at earlier developmental stages (eight and 28 weeks). Development of sex differences in spatial orientation was independent of exposure to pubertal hormones since puberty-blocked and control animals both showed the same pattern of spatial maze performance. This result demonstrates the prenatal nature of spatial orientation development. Furthermore, the unexpected finding that female animals outperformed males in the spatial orientation task, underscores the importance of the testing context in spatial orientation experiments

Peri-pubertal gonadotropin-releasing hormone analog treatment affects hippocampus gene expression without changing spatial orientation in young sheep

Background: Normal brain maturation is the result of molecular changes that can be modulated by endocrine variables associated with brain plasticity and results in sex- and age specific changes in cognitive performance. Using a sheep model, we have previously shown that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) receptors results in increased sex-differences in cognitive executive function and emotional control. In this study we explore effects of this treatment regime on hippocampal gene expression and spatial orientation. Methods: The study was conducted with 30 same-sex twin lambs, half of which were treated with the GnRH analog (GnRHa) goserelin acetate every 4th week, beginning before puberty, until 50 weeks of age. Animals were tested in their spatial orientation ability at 48 weeks of age. Quantitative real time PCR analysis was conducted to examine effects of treatment on the expression of genes associated with synaptic plasticity and endocrine signaling. Results: GnRHa treatment was associated with significant sex- and hemisphere specific changes in mRNA expression for some of the genes studied. The treatment had no significant effect on spatial orientation. However, there was a tendency that females performed better than males in spatial orientation. Conclusion: Our results indicate that GnRH directly and/or indirectly, is involved in the regulation of sex- and side-specific expression patterns of genes. Hence, these results should be considered when long-term peri-pubertal GnRHa treatment is used in children

Ethics Report on Interspecies Somatic Cell Nuclear Transfer Research

This report considers whether research involving the creation of human-animal interspecies somatic cell nuclear transfer (iSCNT) embryos raises new ethical issues, and if so, whether it requires additional or special criteria and oversight distinct from research on human-animal chimeras

Prepubertal gonadotropin-releasing hormone analog leads to exaggerated behavioral and emotional sex differences in sheep

In mammals, sex specialization is reflected by differences in brain anatomy and function. Measurable differences are documented in reproductive behavior, cognition, and emotion. We hypothesized that gonadotropin-releasing hormone (GnRH) plays a crucial role in controlling the extent of the brain's sex specificity and that changes in GnRH action during critical periods of brain development, such as puberty, will result in altered sex-specific behavioral and physiological patterns. We blocked puberty in half of the 48 same-sex Scottish mule Texel cross sheep twins with GnRH analog (GnRHa) goserelin acetate every 3 weeks, beginning just before puberty. To determine the effects of GnRHa treatment on sex-specific behavior and emotion regulation in different social contexts, we employed the food acquisition task (FAT) and measurement of heart rate variability (HRV). ANOVA revealed significant sex and sex × treatment interaction effects, suggesting that treated males were more likely to leave their companions to acquire food than untreated, while the opposite effect was observed in females. Concordant results were seen in HRV; treated males displayed higher HRV than untreated, while the reverse pattern was found in females, as shown by significant sex and sex × treatment interaction effects. We conclude that long-term prepubertal GnRHa treatment significantly affected sex-specific brain development, which impacted emotion and behavior regulation in sheep. These results suggest that GnRH is a modulator of cognitive function in the developing brain and that the sexes are differentially affected by GnRH modulation

Psychoanalysis and bioethics: a Lacanian approach to bioethical discourse

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