The Stressed Gut: Region-specific Immune and Neuroplasticity Changes in Response to Chronic Psychosocial Stress.

Background/aims: Chronic psychological stress affects gastrointestinal physiology which may underpin alterations in the immune response and epithelial transport, both functions are partly regulated by enteric nervous system. However, its effects on enteric neuroplasticity are still unclear. This study aims to investigate the effects of chronic unpredictable psychological stress on intestinal motility and prominent markers of enteric function.

Maternal and early postnatal immune activation produce sex-specific effects on autism-like behaviors and neuroimmune function in mice.

Increasing evidence suggests a role for inflammation in neuropsychiatric conditions including autism spectrum disorder (ASD), a neurodevelopmental syndrome with higher prevalence in males than females. Here we examined the effects of early-life immune system activation (EIA)-comprising regimens of prenatal, early postnatal, or combined ("two-hit") immune activation-on the core behavioral features of ASD (decreased social interaction, increased repetitive behavior, and aberrant communication) in C57BL/6J mice. We treated timed-pregnant mice with polyinosinic:polycytidylic acid (Poly I:C) on gestational day 12.

Maternal and Early Postnatal Immune Activation Produce Dissociable Effects on Neurotransmission in mPFC-Amygdala Circuits.

Inflammatory processes may be involved in the pathophysiology of neuropsychiatric illnesses including autism spectrum disorder (ASD). Evidence from studies in rodents indicates that immune activation during early development can produce core features of ASD (social interaction deficits, dysregulation of communication, increases in stereotyped behaviors, and anxiety), although the neural mechanisms of these effects are not thoroughly understood. We treated timed-pregnant mice with polyinosinic:polycytidylic acid (Poly I:C), which simulates a viral infection, or vehicle on gestational day 12.

Obesity Takes Its Toll on Visceral Pain: High-Fat Diet Induces Toll-Like Receptor 4-Dependent Visceral Hypersensitivity.

Exposure to high-fat diet induces both, peripheral and central alterations in TLR4 expression. Moreover, functional TLR4 is required for the development of high-fat diet-induced obesity. Recently, central alterations in TLR4 expression have been associated with the modulation of visceral pain.

Neural targets in the study and treatment of social cognition in autism spectrum disorder.

The purpose of this chapter is to present results from recent research on social cognition in autism spectrum disorder (ASD). The clinical phenomenology and neuroanatomical circuitry of ASD are first briefly described. The neuropharmacology of social cognition in animal models of ASD and humans is then addressed.

Selective breeding for high anxiety introduces a synonymous SNP that increases neuropeptide S receptor activity.

Neuropeptide S (NPS) has generated substantial interest due to its anxiolytic and fear-attenuating effects in rodents, while a corresponding receptor polymorphism associated with increased NPS receptor (NPSR1) surface expression and efficacy has been implicated in an increased risk of panic disorder in humans. To gain insight into this paradox, we examined the NPS system in rats and mice bred for high anxiety-related behavior (HAB) versus low anxiety-related behavior, and, thereafter, determined the effect of central NPS administration on anxiety- and fear-related behavior. The HAB phenotype was accompanied by lower basal NPS receptor (Npsr1) expression, which we could confirm via in vitro dual luciferase promoter assays.

Toward an immune-mediated subtype of autism spectrum disorder.

A role for immunological involvement in autism spectrum disorder (ASD) has long been hypothesized. This review includes four sections describing (1) evidence for a relationship between familial autoimmune disorders and ASD; (2) results from post-mortem and neuroimaging studies that investigated aspects of neuroinflammation in ASD; (3) findings from animal model work in ASD involving inflammatory processes; and (4) outcomes from trials of anti-inflammatory/immune-modulating drugs in ASD that have appeared in the literature. Following each section, ideas are provided for future research, suggesting paths forward in the continuing effort to define the role of immune factors and inflammation in the pathophysiology of a subtype of ASD.

Toll-like receptor 4 regulates chronic stress-induced visceral pain in mice.

Background: Functional gastrointestinal disorders, which have visceral hypersensitivity as a core symptom, are frequently comorbid with stress-related psychiatric disorders. Increasing evidence points to a key role for toll-like receptor 4 (TLR4) in chronic pain states of somatic origin. However, the central contribution of TLR4 in visceral pain sensation remains elusive.

Ghrelin signalling and obesity: at the interface of stress, mood and food reward.

The neuronal circuitry underlying the complex relationship between stress, mood and food intake are slowly being unravelled and several studies suggest a key role herein for the peripherally derived hormone, ghrelin. Evidence is accumulating linking obesity as an environmental risk factor to psychiatric disorders such as stress, anxiety and depression. Ghrelin is the only known orexigenic hormone from the periphery to stimulate food intake.

Behavioral satiety sequence in a genetic mouse model of obesity: effects of ghrelin receptor ligands.

Behavioral satiety sequence (BSS) is a useful paradigm to assess the effects of orexigenic and anorexigenic profiles of novel pharmacological and genetic manipulations in rodents. To date, no studies have described the satiety profile of leptin-deficient ob/ob mice, an important animal model of obesity in this task. Furthermore, no studies have described changes in the BSS after treatment with ghrelin receptor ligands, which have become an attractive therapeutic target in obesity drug discovery efforts.

Diet-induced obesity blunts the behavioural effects of ghrelin: studies in a mouse-progressive ratio task.

Rational: The ghrelinergic system is implicated in the development of obesity and in modulating central reward systems. It has been reported that diet-induced obesity causes blunted responding on food intake to ghrelin administration, associated with central ghrelin resistance. Here we investigate whether the stimulatory effects of ghrelin on the reward system are altered in diet-induced obese mice.

The temporal impact of chronic intermittent psychosocial stress on high-fat diet-induced alterations in body weight.

Background: Chronic stress and diet can independently or in concert influence the body's homeostasis over time. Thus, it is crucial to investigate the interplay of these parameters to gain insight into the evolution of stress-induced metabolic and eating disorders.

Methods: C57BL/6J mice were subjected to chronic psychosocial (mixed model of social defeat and overcrowding) stress in combination with either a high- or low-fat diet for three or six weeks.

Neuropeptide S alters anxiety, but not depression-like behaviour in Flinders Sensitive Line rats: a genetic animal model of depression.

Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behaviour in rodents. However, little knowledge is available regarding the NPS system in depression-related behaviours, and whether NPS also exerts anxiolytic effects in an animal model of psychopathology. Therefore, the aim of this work was to characterize the effects of NPS on depression- and anxiety-related parameters, using male and female rats in a well-validated animal model of depression: the Flinders Sensitive Line (FSL), their controls, the Flinders Resistant Line (FRL), and Sprague-Dawley (SD) rats.

Is there altered sensitivity to ghrelin-receptor ligands in leptin-deficient mice?: importance of satiety state and time of day.

Background: Several fine-tuned and interconnected hypothalamic peptidergic systems orchestrate the regulation of energy homeostasis in the body. The orexigenic peptide ghrelin and the anorexigenic peptide leptin are among the most important, and both have been implicated in the development of eating disorders from obesity to anorexia nervosa.

Objectives: The goal of these studies was to examine the response of leptin-deficient ob/ob mice in ghrelin-receptor ligands in a food intake task.

Progressive ratio responding in an obese mouse model: Effects of fenfluramine.

The progressive ratio schedule of operant responding is a well utilised task for assessing the rewarding aspects of abused drugs and natural rewards including food. Interestingly, progressive ratio paradigms have mainly been neglected in the field of animal research in obesity. Among the most widely studied mouse models of obesity is the leptin-deficient ob/ob mouse, characterised by hyperphagia and obesity.

Leptin-deficient mice retain normal appetitive spatial learning yet exhibit marked increases in anxiety-related behaviours.

Rationale: The individual's emotional state influences food intake in both humans and rodents. Moreover, specific cognitive processes regulating the salient aspects of food reward are also critical for ingestive behaviour. However, the molecular mechanisms underlying such influence remain unclear.

Metabotropic glutamate receptor 7: at the interface of cognition and emotion.

Understanding the complex interaction between stress and genetics that leads to the manifestation of disorders such as depression, anxiety, and cognitive dysfunction is one of the key areas of research in modern neuroscience. Growing evidence suggests that the glutamatergic system may be a relevant therapeutic target for such disorders. Glutamate is the neurotransmitter at the vast majority of excitatory synapses in the brain, and metabotropic glutamate (mGlu) receptor subtypes (mGlu(1) receptor-mGlu(8) receptor) act as important pre- and postsynaptic regulators of neurotransmission in the central nervous system (CNS), providing a mechanism by which fast synaptic responses through ligand-gated cation channels can be fine-tuned.