How age, sex and genotype shape the stress response

Exposure to chronic stress is a leading pre-disposing factor for several neuropsychiatric disorders as it often leads to maladaptive responses. The response to stressful events is heterogeneous, underpinning a wide spectrum of distinct changes amongst stress-exposed individuals'. Several factors can underlie a different perception to stressors and the setting of distinct coping strategies that will lead to individual differences on the susceptibility/resistance to stress. Beyond the factors related to the stressor itself, such as intensity, duration or predictability, there are factors intrinsic to the individuals that are relevant to shape the stress response, such as age, sex and genetics. In this review, we examine the contribution of such intrinsic factors to the modulation of the stress response based on experimental rodent models of response to stress and discuss to what extent that knowledge can be potentially translated to humans.FEDER through the Operational Programme Competitiveness Factors - COMPETE and National Funds through FCT - Foundation for Science and Technology under the project POCI-01-0145-FEDER-007038; and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE, 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). We acknowledge the Portuguese Foundation for Science and Technology (FCT) for providing a post-doctoral fellowship to SR (SFRH/BPD/72710/2010), a doctoral fellowship to SM (SFRH/BD/69311/2010) and a fellowship to AN (ANR/NEU-OSD/0258/2012)info:eu-repo/semantics/publishedVersio

Impact of chronic stress protocols in learning and memory in rodents: systematic review and meta-analysis

The idea that maladaptive stress impairs cognitive function has been a cornerstone of decades in basic and clinical research. However, disparate findings have reinforced the need to aggregate results from multiple sources in order to confirm the validity of such statement. In this work, a systematic review and meta-analyses were performed to aggregate results from rodent studies investigating the impact of chronic stress on learning and memory. Results obtained from the included studies revealed a significant effect of stress on global cognitive performance. In addition, stressed rodents presented worse consolidation of learned memories, although no significantly differences between groups at the acquisition phase were found. Despite the methodological heterogeneity across studies, these effects were independent of the type of stress, animals' strains or age. However, our findings suggest that stress yields a more detrimental effect on spatial navigation tests' performance. Surprisingly, the vast majority of the selected studies in this field did not report appropriate statistics and were excluded from the quantitative analysis. We have therefore purposed a set of guidelines termed PROBE (Preferred Reporting Orientations for Behavioral Experiments) to promote an adequate reporting of behavioral experiments.This work was funded by the European Commission (FP7) "SwitchBox" (Contract HEALTH-F2-2010-259772) project and co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER), and by Fundacao Calouste Gulbenkian (Portugal) (Contract grant number: P-139977; project "Better mental health during ageing based on temporal prediction of individual brain ageing trajectories (TEMPO)"). PSM is supported by an FCT fellowship grant, from the PhD-iHES program, with the reference PDE/BDE/113601/2015.info:eu-repo/semantics/publishedVersio

Relevance of Stress and Female Sex Hormones for Emotion and Cognition

There are clear sex differences in incidence and onset of stress-related and other psychiatric disorders in humans. Yet, rodent models for psychiatric disorders are predominantly based on male animals. The strongest argument for not using female rodents is their estrous cycle and the fluctuating sex hormones per phase which multiplies the number of animals to be tested. Here, we will discuss studies focused on sex differences in emotionality and cognitive abilities in experimental conditions with and without stress. First, female sex hormones such as estrogens and progesterone affect emotions and cognition, contributing to sex differences in behavior. Second, females respond differently to stress than males which might be related to the phase of the estrous cycle. For example, female rats and mice express less anxiety than males in a novel environment. Proestrus females are less anxious than females in the other estrous phases. Third, males perform in spatial tasks superior to females. However, while stress impairs spatial memory in males, females improve their spatial abilities, depending on the task and kind of stressor. We conclude that the differences in emotion, cognition and responses to stress between males and females over the different phases of the estrous cycle should be used in animal models for stress-related psychiatric disorders

Factors Influencing Individual Variation in Farm Animal Cognition and How to Account for These Statistically

For farmed species, good health and welfare is a win-win situation: both the animals and producers can benefit. In recent years, animal welfare scientists have embraced cognitive sciences to rise to the challenge of determining an animal's internal state in order to better understand its welfare needs and by extension, the needs of larger groups of animals. A wide range of cognitive tests have been developed that can be applied in farmed species to assess a range of cognitive traits. However, this has also presented challenges. Whilst it may be expected to see cognitive variation at the species level, differences in cognitive ability between and within individuals of the same species have frequently been noted but left largely unexplained. Not accounting for individual variation may result in misleading conclusions when the results are applied both at an individual level and at higher levels of scale. This has implications both for our fundamental understanding of an individual's welfare needs, but also more broadly for experimental design and the justification for sample sizes in studies using animals. We urgently need to address this issue. In this review, we will consider the latest developments on the causes of individual variation in cognitive outcomes, such as the choice of cognitive test, sex, breed, age, early life environment, rearing conditions, personality, diet, and the animal's microbiome. We discuss the impact of each of these factors specifically in relation to recent work in farmed species, and explore the future directions for cognitive research in this field, particularly in relation to experimental design and analytical techniques that allow individual variation to be accounted for appropriately