GG soluble mediators ameliorate early life stress-induced visceral hypersensitivity and changes in spinal cord gene expression.

Visceral hypersensitivity is a hallmark of many functional and stress-related gastrointestinal disorders, and there is growing evidence that the gut microbiota may play a role in its pathophysiology. It has previously been shown that early life stress-induced visceral sensitivity is reduced by various probiotic strains of bacteria (including Lactobacillus rhamnosus GG (LGG)) alone or in combination with prebiotic fibres in rat models. However, the exact mechanisms underpinning such effects remain unresolved.

Enduring Behavioral Effects Induced by Birth by Caesarean Section in the Mouse.

Birth by Caesarean (C)-section impacts early gut microbiota colonization and is associated with an increased risk of developing immune and metabolic disorders. Moreover, alterations of the microbiome have been shown to affect neurodevelopmental trajectories. However, the long-term effects of C-section on neurobehavioral processes remain unknown.

Enduring effects of an unhealthy diet during adolescence on systemic but not neurobehavioural measures in adult rats.

Adolescence is an important stage of maturation for various brain structures. It is during this time therefore that the brain may be more vulnerable to environmental factors such as diet that may influence mood and memory. Diets high in fat and sugar (termed a cafeteria diet) during adolescence have been shown to negatively impact upon cognitive performance, which may be reversed by switching to a standard diet during adulthood.

A role for the orphan nuclear receptor TLX in the interaction between neural precursor cells and microglia.

Microglia are an essential component of the neurogenic niche in the adult hippocampus and are involved in the control of neural precursor cell (NPC) proliferation, differentiation and the survival and integration of newborn neurons in hippocampal circuitry. Microglial and neuronal cross-talk is mediated in part by the chemokine fractalkine/chemokine (C-X3-C motif) ligand 1 (CX3CL1) released from neurons, and its receptor CX3C chemokine receptor 1 (CX3CR1) which is expressed on microglia. A disruption in this pathway has been associated with impaired neurogenesis yet the specific molecular mechanisms by which this interaction occurs remain unclear.

Host Microbiota Regulates Central Nervous System Serotonin Receptor 2C Editing in Rodents.

Microbial colonization of the gastrointestinal tract plays a crucial role in the development of enteric and central nervous system functionality. The serotonergic system has been heavily implicated in microbiota-gut-brain axis signaling, particularly in proof-of-principle studies in germ-free (GF) animals. One aspect of the serotonergic system that has been left unexplored in relation to the microbiota is the unique ability of the serotonin receptor 2C (5-HT) to undergo post-transcriptional editing, which has been implicated in decreased receptor functionality.

Differential effects of adolescent and adult-initiated exercise on cognition and hippocampal neurogenesis.

Adolescence is a critical period for postnatal brain maturation and thus a time when environmental influences may affect cognitive processes in later life. Exercise during adulthood has been shown to increase hippocampal neurogenesis and enhance cognition. However, the impact of exercise initiated in adolescence on the brain and behavior in adulthood is not fully understood.

Chronic interleukin-1β in the dorsal hippocampus impairs behavioural pattern separation.

Understanding the long-term consequences of chronic inflammation in the hippocampus may help to develop therapeutic targets for the treatment of cognitive disorders related to stress, ageing and neurodegeneration. The hippocampus is particularly vulnerable to increases in the pro-inflammatory cytokine interleukin-1β (IL-1β), a mediator of neuroinflammation, with elevated levels implicated in the aetiology of neurodegenerative diseases such as Alzheimer's and Parkinson's, and in stress-related disorders such as depression. Acute increases in hippocampal IL-1β have been shown to impair cognition and reduce adult hippocampal neurogenesis, the birth of new neurons.

Social interaction-induced activation of RNA splicing in the amygdala of microbiome-deficient mice.

Social behaviour is regulated by activity of host-associated microbiota across multiple species. However, the molecular mechanisms mediating this relationship remain elusive. We therefore determined the dynamic, stimulus-dependent transcriptional regulation of germ-free (GF) and GF mice colonised post weaning (exGF) in the amygdala, a brain region critically involved in regulating social interaction.

Differential effects of adolescent and adult-initiated voluntary exercise on context and cued fear conditioning.

Adolescence is a critical period for postnatal brain maturation and a time during which there is increased susceptibility to developing emotional and cognitive-related disorders. Exercise during adulthood has been shown to increase hippocampal plasticity and enhance cognition. However, the impact of exercise initiated in adolescence, on brain and behaviour in adulthood is not yet fully explored or understood.

The orphan nuclear receptor TLX regulates hippocampal transcriptome changes induced by IL-1β.

TLX is an orphan nuclear receptor highly expressed within neural progenitor cells (NPCs) in the hippocampus where is regulates proliferation. Inflammation has been shown to have negative effects on hippocampal function as well as on NPC proliferation. Specifically, the pro-inflammatory cytokine IL-1β suppresses NPC proliferation as well as TLX expression in the hippocampus.

Neurobehavioural effects of Lactobacillus rhamnosus GG alone and in combination with prebiotics polydextrose and galactooligosaccharide in male rats exposed to early-life stress.

Early life is a period of significant brain development when the brain is at its most plastic and vulnerable. Stressful episodes during this window of development have long-lasting effects on the central nervous system. Rodent maternal separation (MS) is a reliable model of early-life stress and induces alterations in both physiology and behaviour.

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling.

The amygdala is a key brain area regulating responses to stress and emotional stimuli, so improving our understanding of how it is regulated could offer novel strategies for treating disturbances in emotion regulation. As we review here, a growing body of evidence indicates that the gut microbiota may contribute to a range of amygdala-dependent brain functions from pain sensitivity to social behavior, emotion regulation, and therefore, psychiatric health. In addition, it appears that the microbiota is necessary for normal development of the amygdala at both the structural and functional levels.

TLX is an intrinsic regulator of the negative effects of IL-1β on proliferating hippocampal neural progenitor cells.

Hippocampal neurogenesis is a lifelong process whereby new neurons are produced and integrate into the host circuitry within the hippocampus. It is regulated by a multitude of extrinsic and intrinsic regulators and is believed to contribute to certain hippocampal-dependent cognitive tasks. Hippocampal neurogenesis and associated cognition have been demonstrated to be impaired after increases in the levels of proinflammatory cytokine IL-1β in the hippocampus, such as that which occurs in various neurodegenerative and psychiatric disorders.

Microbial regulation of microRNA expression in the amygdala and prefrontal cortex.

Background: There is growing evidence for a role of the gut microbiome in shaping behaviour relevant to many psychiatric and neurological disorders. Preclinical studies using germ-free (GF) animals have been essential in contributing to our current understanding of the potential importance of the host microbiome for neurodevelopment and behaviour. In particular, it has been repeatedly demonstrated that manipulation of the gut microbiome modulates anxiety-like behaviours.

Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat.

The gut microbiota interacts with the host via neuroimmune, neuroendocrine and neural pathways. These pathways are components of the brain-gut-microbiota axis and preclinical evidence suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, function and behaviour. The pathophysiology of depression involves neuroimmune-neuroendocrine dysregulation.

Microbes & neurodevelopment--Absence of microbiota during early life increases activity-related transcriptional pathways in the amygdala.

The mammalian amygdala is a key emotional brain region for eliciting social behaviour, critically involved in anxiety and fear-related behaviours, and hence a focus of research on neurodevelopmental and stress-related disorders such as autism and anxiety. Recently, increasing evidence implicates host-microbe interactions in the aetiology of these conditions. Germ-free (GF) mice, devoid of any microbiota throughout organismal maturation, are a well-established tool to study the effects of absence of the microbiota on host physiology.

Thinking small: towards microRNA-based therapeutics for anxiety disorders.

Introduction: Anxiety disorders are the most frequently diagnosed psychiatric conditions, negatively affecting quality of life and creating a significant economic burden. These complex disorders are extremely difficult to treat, and there is a great need for novel therapeutics with greater efficacy and minimal adverse side effects.

Areas Covered: In this review, the authors describe the role that microribonucleic acids (microRNA or miRNA) play in the development of anxiety disorders and their potential to serve as biomarkers of disease as well as targets for pharmacological treatment.