Localization of Mineralocorticoid Receptors at Mammalian Synapses

In the brain, membrane associated nongenomic steroid receptors can induce fast-acting responses to ion conductance and second messenger systems of neurons. Emerging data suggest that membrane associated glucocorticoid and mineralocorticoid receptors may directly regulate synaptic excitability during times of stress when adrenal hormones are elevated. As the key neuron signaling interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. The lateral amygdala is a key site for synaptic plasticity underlying conditioned fear, which can both trigger and be coincident with the stress response. A large body of electrophysiological data shows rapid regulation of neuronal excitability by steroid hormone receptors. Despite the importance of these receptors, to date, only the glucocorticoid receptor has been anatomically localized to the membrane. We investigated the subcellular sites of mineralocorticoid receptors in the lateral amygdala of the Sprague-Dawley rat. Immunoblot analysis revealed the presence of mineralocorticoid receptors in the amygdala. Using electron microscopy, we found mineralocorticoid receptors expressed at both nuclear including: glutamatergic and GABAergic neurons and extra nuclear sites including: presynaptic terminals, neuronal dendrites, and dendritic spines. Importantly we also observed mineralocorticoid receptors at postsynaptic membrane densities of excitatory synapses. These data provide direct anatomical evidence supporting the concept that, at some synapses, synaptic transmission is regulated by mineralocorticoid receptors. Thus part of the stress signaling response in the brain is a direct modulation of the synapse itself by adrenal steroids

Scoping review of indicators and methods of measurement used to evaluate the impact of dog population management interventions

Background: Dogs are ubiquitous in human society and attempts to manage their populations are common to most countries. Managing dog populations is achieved through a range of interventions to suit the dog population dynamics and dog ownership characteristics of the location, with a number of potential impacts or goals in mind. Impact assessment provides the opportunity for interventions to identify areas of inefficiencies for improvement and build evidence of positive change. Methods: This scoping review collates 26 studies that have assessed the impacts of dog population management interventions. Results: It reports the use of 29 indicators of change under 8 categories of impact and describes variation in the methods used to measure these indicators. Conclusion: The relatively few published examples of impact assessment in dog population management suggest this field is in its infancy; however this review highlights those notable exceptions. By describing those indicators and methods of measurement that have been reported thus far, and apparent barriers to efficient assessment, this review aims to support and direct future impact assessment

Qualitative Evaluation of the Five-Year ‘Red Collar’ Campaign to End Inhumane Culling of Dogs as a Method of Rabies Control

Dog-mediated human rabies can be eliminated through mass dog vaccination. Despite leading authorities in human and animal health uniting to advance effective and humane rabies control, some governments resort to lethal methods, which are unethical, often inhumane and ineffective. To end the inhumane culling of dogs in response to rabies, World Animal Protection launched ‘Red Collar’; a five-year campaign (2011–2016) that worked with governments to promote the implementation of mass dog vaccination for rabies control. We present the findings from a qualitative evaluation of ‘Red Collar’, conducted both regionally and with national focus on Bangladesh, China, Indonesia, the Philippines and Zanzibar, Tanzania. Through semi-structured interviews and written contributions from stakeholders (n = 54), we compared perceptions of changes with stated campaign goals to capture recommendations for future work. The campaign successfully generated momentum for implementation of mass dog vaccination by targeted governments. Lessons learned were established: Value of a consistent animal welfare ‘voice’; the need to explore the motivations behind culling; the need to capacity build; time required for the ‘ripple effect’ to inspire humane control in other countries; importance of monitoring and evaluation of indicators; time and effort required for exit strategies and prior preparation for a robust response to culling

Welfare of primates in laboratories: opportunities for refinement

The use of primates in regulated research and testing means that they are intentionally subjected to scientific procedures that have the potential to cause pain, suffering, distress, or lasting harm. These harms, combined with keeping primates in restricted laboratory conditions, are balanced against the potential (primarily human) benefits gained from their use. In this chapter, we provide a brief overview of the use of primates in laboratories, the estimated number and purpose of use, and summarize the evidence that primates are especially vulnerable and deserve special protection compared to other animals. The 3Rs (Replacement, Reduction and Refinement) framework, underpinning humane science, is described, and we emphasize both the ethical and scientific need for Refinement. Refinement refers to all approaches used (by humans responsible for their care) to minimize harms and improve welfare for those primates that are still used in research after the application of the Replacement and Reduction principles. There is a growing body of evidence demonstrating an interplay between animals’ welfare and experimental parameters, and that this interplay affects the validity and reliability of scientific output. With this perspective, we argue that it is better to collect no data than to collect poor (e.g. invalid, unreliable) data. It is, after all, unacceptable for primates to suffer in vain and violates utilitarian principles underlying animal use. Furthermore, inconsistency in experimental approach may introduce conflicting results, increasing the likelihood of using more animals, and delaying delivery of promising therapies to the clinic. We focus on mitigating the major welfare issues faced by primates housed in laboratories through coordinated refinements across their lifespans. Drawing on examples from cynomolgus macaques (Macaca fascicularis), an Old World monkey commonly used during the development of medical products, we highlight the importance of understanding the critical role humans play in the laboratory, providing environments, performing husbandry, and undertaking procedures that promote welfare and decrease harms. Our theoretical premise is that if primates are to be ‘fit for purpose’ (i.e. well suited for the designated role), we need a proactive, concerted approach for implementing Refinement that spans their lifetime.Output Status: Forthcomin

Welfare of primates in laboratories: opportunities for refinement

The use of primates in regulated research and testing means that they are intentionally subjected to scientific procedures that have the potential to cause pain, suffering, distress, or lasting harm. These harms, combined with keeping primates in restricted laboratory conditions, are balanced against the potential (primarily human) benefits gained from their use. In this chapter, we provide a brief overview of the use of primates in laboratories, the estimated number and purpose of use, and summarize the evidence that primates are especially vulnerable and deserve special protection compared to other animals. The 3Rs (Replacement, Reduction and Refinement) framework, underpinning humane science, is described, and we emphasize both the ethical and scientific need for Refinement. Refinement refers to all approaches used (by humans responsible for their care) to minimize harms and improve welfare for those primates that are still used in research after the application of the Replacement and Reduction principles. There is a growing body of evidence demonstrating an interplay between animals’ welfare and experimental parameters, and that this interplay affects the validity and reliability of scientific output. With this perspective, we argue that it is better to collect no data than to collect poor (e.g. invalid, unreliable) data. It is, after all, unacceptable for primates to suffer in vain and violates utilitarian principles underlying animal use. Furthermore, inconsistency in experimental approach may introduce conflicting results, increasing the likelihood of using more animals, and delaying delivery of promising therapies to the clinic. We focus on mitigating the major welfare issues faced by primates housed in laboratories through coordinated refinements across their lifespans. Drawing on examples from cynomolgus macaques (Macaca fascicularis), an Old World monkey commonly used during the development of medical products, we highlight the importance of understanding the critical role humans play in the laboratory, providing environments, performing husbandry, and undertaking procedures that promote welfare and decrease harms. Our theoretical premise is that if primates are to be ‘fit for purpose’ (i.e. well suited for the designated role), we need a proactive, concerted approach for implementing Refinement that spans their lifetime