Comparative placentation in laboratory animals A review

Many structural and functional differences between various placentas of laboratory animals are pointed out with emphasis on the two major groups, namely hemochorial and non-hemochorial types of placentation. This should be considered when species are selected for experiments involving placenta

Differences in adaptive abilities of three breeds of Chinese pigs. Behavioural and neuroendocrine studies

International audienc

Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions.

Inflammatory cytokines are commonly elevated in acute depression and are associated with resistance to monoaminergic treatment. To examine the potential role of cytokines in the pathogenesis and treatment of depression, we carried out a systematic review and meta-analysis of antidepressant activity of anti-cytokine treatment using clinical trials of chronic inflammatory conditions where depressive symptoms were measured as a secondary outcome. Systematic search of the PubMed, EMBASE, PsycINFO and Cochrane databases, search of reference lists and conference abstracts, followed by study selection process yielded 20 clinical trials. Random effect meta-analysis of seven randomised controlled trials (RCTs) involving 2370 participants showed a significant antidepressant effect of anti-cytokine treatment compared with placebo (standardised mean difference (SMD)=0.40, 95% confidence interval (CI), 0.22-0.59). Anti-tumour necrosis factor drugs were most commonly studied (five RCTs); SMD=0.33 (95% CI; 0.06-0.60). Separate meta-analyses of two RCTs of adjunctive treatment with anti-cytokine therapy and eight non-randomised and/or non-placebo studies yielded similar small-to-medium effect estimates favouring anti-cytokine therapy; SMD=0.19 (95% CI, 0.00-0.37) and 0.51 (95% CI, 0.34-0.67), respectively. Adalimumab, etanercept, infliximab and tocilizumab all showed statistically significant improvements in depressive symptoms. Meta-regression exploring predictors of response found that the antidepressant effect was associated with baseline symptom severity (P=0.018) but not with improvement in primary physical illness, sex, age or study duration. The findings indicate a potentially causal role for cytokines in depression and that cytokine modulators may be novel drugs for depression in chronically inflamed subjects. The field now requires RCTs of cytokine modulators using depression as the primary outcome in subjects with high inflammation who are free of other physical illnesses.Molecular Psychiatry advance online publication, 18 October 2016; doi:10.1038/mp.2016.167

Immunopsychiatry: important facts

Accumulating evidence indicate a role for the immune system particularly inflammation and autoimmunity in the aetiology of major psychiatric disorders such as depression and schizophrenia. In this paper, we discuss some of the key advances in immunopsychiatry in order to highlight to psychiatrists and other health professionals how an increased understanding of this field might enhance our knowledge of illness mechanism and approaches to treatment. We present a brief overview of clinical research that link inflammation and autoimmunity with depression and psychosis, including potential role of inflammation in treatment response, current evidence for the effectiveness of immune-modulating treatment for depression and psychosis, and possible role of inflammation in common physical comorbidities for these disorders such as coronary heart disease and diabetes mellitus. Gaining a better understanding of the role of immune system could be paradigm changing for psychiatry. We need collaborations between clinicians and scientists to deliver high-quality translational research in order to fully realise the clinical potential of this exciting and rapidly expanding field.GMK is supported by an Intermediate Clinical Fellowship from the Wellcome Trust (201486/Z/16/Z) and a Clinical Lecturer Starter Grant from the Academy of Medical Sciences, UK (grant no. 80354). PBJ acknowledges grant support from the Wellcome Trust (095844/Z/11/Z & 088869/Z/09/Z) and NIHR (RP-PG-0606–1335, Cambridge Biomedical Research Centre and CLAHRC East of England). RD has received grants from the National Institute of Neurological Diseases and Stroke of the National Institutes of Health (grants R01 NS073939; R01 NS074999), the National Cancer Institute (R01CA193522) and the National Institute of Mental Health (R21MH104694)

Physiological stress and spatio-temporal fluctuations of food abundance and population density in Eurasian red squirrels

In continuously changing environments, variation of different ecological factors could affect the functioning of the hypothalamic-pituitary-adrenal (HPA) axis in wild mammals, increasing the secretion of glucocorticoids (GCs). In different animal species, GC concentrations are often used as a measure of the physiological stress response to environmental pressures, such as fluctuations in food abundance, population density, intra-and interspecific competition, and predation risk. However, previous studies reported contrasting results or did not find clear associations between physiological stress and environmental variables. Here, we used concentrations of faecal glucocorticoid metabolites (FGMs) as an integrated measure of physiological stress in wild Eurasian red squirrels (Sciurus vulgaris) from three study areas in the Italian Alps, to investigate whether variations in conifer-seed crop size and/or population density affected HPA axis activity. Squirrel density was estimated in each trapping session using the minimum number of animals alive, and annual counts of fresh cones from different conifer species were used to estimate annual food abundance (MJ/ha). We expected higher FGMs in response to increasing population density and/or decreasing food abundance, since these two variables could act as environmental stressors. Our results showed a lack of association between population density and FGMs and a significant effect of food abundance on FGMs. When conifer seed-crops were poor to moderate, FGMs increased with food abundance, while in the range of high seed-crops, FGMs remained first constant and then slightly decreased with a further increase in seed abundance. We also found differences in FGMs among seasons, as previously observed in this species. Our study adds further evidence that physiological stress can be influenced in different ways by environmental pressures and that long-term studies using individually marked animals are needed to disentangle the potential adaptive outcome of the physiological stress response in pulsed resource systems

Voluntary Wheel Running Reverses Age-Induced Changes in Hippocampal Gene Expression

Normal aging alters expression of numerous genes within the brain. Some of these transcription changes likely contribute to age-associated cognitive decline, reduced neural plasticity, and the higher incidence of neuropathology. Identifying factors that modulate brain aging is crucial for improving quality of life. One promising intervention to counteract negative effects of aging is aerobic exercise. Aged subjects that exercise show enhanced cognitive performance and increased hippocampal neurogenesis and synaptic plasticity. Currently, the mechanisms behind the anti-aging effects of exercise are not understood. The present study conducted a microarray on whole hippocampal samples from adult (3.5-month-old) and aged (18-month-old) male BALB/c mice that were individually housed with or without running wheels for 8 weeks. Results showed that aging altered genes related to chromatin remodeling, cell growth, immune activity, and synapse organization compared to adult mice. Exercise was found to modulate many of the genes altered by aging, but in the opposite direction. For example, wheel running increased expression of genes related to cell growth and attenuated expression of genes involved in immune function and chromatin remodeling. Collectively, findings show that even late-onset exercise may attenuate age-related changes in gene expression and identifies possible pathways through which exercise may exert its beneficial effects

Mechanisms of poststroke fatigue

Poststroke fatigue is a debilitating symptom and is poorly understood. Here we summarise molecular, behavioural and neurophysiological changes related to poststroke fatigue and put forward potential theories for mechanistic understanding of poststroke fatigue

MutDB: update on development of tools for the biochemical analysis of genetic variation

Understanding how genetic variation affects the molecular function of gene products is an emergent area of bioinformatic research. Here, we present updates to MutDB (http://www.mutdb.org), a tool aiming to aid bioinformatic studies by integrating publicly available databases of human genetic variation with molecular features and clinical phenotype data. MutDB, first developed in 2002, integrates annotated SNPs in dbSNP and amino acid substitutions in Swiss-Prot with protein structural information, links to scores that predict functional disruption and other useful annotations. Though these functional annotations are mainly focused on nonsynonymous SNPs, some information on other SNP types included in dbSNP is also provided. Additionally, we have developed a new functionality that facilitates KEGG pathway visualization of genes containing SNPs and a SNP query tool for visualizing and exporting sets of SNPs that share selected features based on certain filters

Optimisation of energetic and reproductive gains explains behavioural responses to environmental variation across seasons and years

Animals switch between inactive and active states, simultaneously impacting their energy intake, energy expenditure and predation risk, and collectively defining how they engage with environmental variation and trophic interactions. We assess daily activity responses to long‐term variation in temperature, resources and mating opportunities to examine whether individuals choose to be active or inactive according to an optimisation of the relative energetic and reproductive gains each state offers. We show that this simplified behavioural decision approach predicts most activity variation (R2 = 0.83) expressed by free‐ranging red squirrels over 4 years, as quantified through accelerometer recordings (489 deployments; 5066 squirrel‐days). Recognising activity as a determinant of energetic status, the predictability of activity variation aggregated at a daily scale, and the clear signal that behaviour is environmentally forced through optimisation of gain, provides an integrated approach to examine behavioural variation as an intermediary between environmental variation and energetic, life‐history and ecological outcomes.By assessing daily activity responses to long‐term variation in temperature, resources, and mating opportunities, we examine whether individuals choose to be active or inactive according to an optimization of energetic and reproductive gains. This simplified behavioural decision approach predicts most daily activity variation (R2 = 0.83) expressed by free‐ranging red squirrels over four years, as quantified through accelerometer recordings. Here we provide an integrated approach to examine behavioural variation as an intermediary between environmental variation and energetic, life‐history, and ecological outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154889/1/ele13494_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154889/2/ele13494.pd

Serum kynurenic acid is reduced in affective psychosis

A subgroup of individuals with mood and psychotic disorders shows evidence of inflammation that leads to activation of the kynurenine pathway and the increased production of neuroactive kynurenine metabolites. Depression is hypothesized to be causally associated with an imbalance in the kynurenine pathway, with an increased metabolism down the 3-hydroxykynurenine (3HK) branch of the pathway leading to increased levels of the neurotoxic metabolite, quinolinic acid (QA), which is a putative Nmethyl- D-aspartate (NMDA) receptor agonist. In contrast, schizophrenia and psychosis are hypothesized to arise from increased metabolism of the NMDA receptor antagonist, kynurenic acid (KynA), leading to hypofunction of GABAergic interneurons, the disinhibition of pyramidal neurons and striatal hyperdopaminergia. Here we present results that challenge the model of excess KynA production in affective psychosis. After rigorous control of potential confounders and multiple testing we find significant reductions in serum KynA and/or KynA/QA in acutely ill inpatients with major depressive disorder (N = 35), bipolar disorder (N = 53) and schizoaffective disorder (N = 40) versus healthy controls (N = 92). No significant difference was found between acutely ill inpatients with schizophrenia (n = 21) and healthy controls. Further, a post hoc comparison of patients divided into the categories of non-psychotic affective disorder, affective psychosis and psychotic disorder (non-affective) showed that the greatest decrease in KynA was in the affective psychosis group relative to the other diagnostic groups. Our results are consistent with reports of elevations in proinflammatory cytokines in psychosis, and preclinical work showing that inflammation upregulates the enzyme, kynurenine mono-oxygenase (KMO), which converts kynurenine into 3-hydroxykynurenine and quinolinic acid