A gut reaction? The role of the microbiome in aggression.

Recent research has unveiled conflicting evidence regarding the link between aggression and the gut microbiome. Here, we compared behavior profiles of control, germ-free (GF), and antibiotic-treated mice, as well as re-colonized GF mice to understand the impact of the gut microbiome on aggression using the resident-intruder paradigm. Our findings revealed a link between gut microbiome depletion and higher aggression, accompanied by notable changes in urine metabolite profiles and brain gene expression.

Psilocybin induces acute anxiety and changes in amygdalar phosphopeptides independently from the 5-HT2A receptor.

Psilocybin, and its metabolite psilocin, induces psychedelic effects through activation of the 5-HT2A receptor. Psilocybin has been proposed as a treatment for depression and anxiety but sometimes induces anxiety in humans. An understanding of mechanisms underlying the anxiety response will help to better develop therapeutic prospects of psychedelics.

Bacteroides is increased in an autism cohort and induces autism-relevant behavioral changes in mice in a sex-dependent manner.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition which is defined by decreased social communication and the presence of repetitive or stereotypic behaviors. Recent evidence has suggested that the gut-brain axis may be important in neurodevelopment in general and may play a role in ASD in particular. Here, we present a study of the gut microbiome in 96 individuals diagnosed with ASD in Israel, compared to 42 neurotypical individuals.

CHD8 regulates gut epithelial cell function and affects autism-related behaviors through the gut-brain axis.

Autism is a neurodevelopmental disorder characterized by early-onset social behavioral deficits and repetitive behaviors. Chromodomain helicase DNA-binding protein (CHD8) is among the genes most strongly associated with autism. In addition to the core behavioral symptoms of autism, affected individuals frequently present with gastrointestinal symptoms that are also common among individuals harboring mutations in the gene encoding CHD8.

CTCF in parvalbumin-expressing neurons regulates motor, anxiety and social behavior and neuronal identity.

CCCTC-binding factor (CTCF) is a regulator of chromatin organization and has direct effects on gene transcription. Mutations in CTCF have been identified in individuals with neurodevelopmental conditions. There are wide range of behaviors associated with these mutations, including intellectual disabilities, changes in temperament, and autism.

Gestational diabetes induces behavioral and brain gene transcription dysregulation in adult offspring.

The etiology of Autism Spectrum Disorders (ASD) includes a strong genetic component and a complicated environmental component. Recent evidence indicates that maternal diabetes, including gestational diabetes, is associated with an increased prevalence of ASD. While previous studies have looked into possible roles for maternal diabetes in neurodevelopment, there are few studies into how gestational diabetes, with no previous diabetic or metabolic phenotype, may affect neurodevelopment.

Gene network analysis reveals a role for striatal glutamatergic receptors in dysregulated risk-assessment behavior of autism mouse models.

Autism spectrum disorder (ASD) presents a wide, and often varied, behavioral phenotype. Improper assessment of risks has been reported among individuals diagnosed with ASD. Improper assessment of risks may lead to increased accidents and self-injury, also reported among individuals diagnosed with ASD.

Antidepressants affect gut microbiota and Ruminococcus flavefaciens is able to abolish their effects on depressive-like behavior.

Accumulating evidence demonstrates that the gut microbiota affects brain function and behavior, including depressive behavior. Antidepressants are the main drugs used for treatment of depression. We hypothesized that antidepressant treatment could modify gut microbiota which can partially mediate their antidepressant effects.

Dysbiosis of microbiome and probiotic treatment in a genetic model of autism spectrum disorders.

Recent studies have determined that the microbiome has direct effects on behavior, and may be dysregulated in neurodevelopmental conditions. Considering that neurodevelopmental conditions, such as autism, have a strong genetic etiology, it is necessary to understand if genes associated with neurodevelopmental disorders, such as Shank3, can influence the gut microbiome, and if probiotics can be a therapeutic tool. In this study, we have identified dysregulation of several genera and species of bacteria in the gut and colon of both male and female Shank3 KO mice.

Differential contribution of cis and trans gene transcription regulatory mechanisms in amygdala and prefrontal cortex and modulation by social stress.

While both individual transcription factors and cis-acting sites have been studied in relation to psychiatric disorders, there is little knowledge of the relative contribution of trans-acting and cis-acting factors to gene transcription in the brain. Using an RNA-seq approach in mice bred from two evolutionary-distinct mice strains, we determined the contribution of cis and trans factors to gene expression in the prefrontal cortex and amygdala, two regions of the brain relevant to the stress response, and the contribution of cis and trans factors in the prefrontal cortex after Chronic Social Defeat (CSD) in mice. More genes were regulated by cis-regulatory factors in both brain regions, underlying the importance of cis-acting gene regulation in the brain.

Neuronal CTCF Is Necessary for Basal and Experience-Dependent Gene Regulation, Memory Formation, and Genomic Structure of BDNF and Arc.

CCCTC-binding factor (CTCF) is an organizer of higher-order chromatin structure and regulates gene expression. Genetic studies have implicated mutations in CTCF in intellectual disabilities. However, the role of CTCF-mediated chromatin structure in learning and memory is unclear.

Sodium butyrate attenuates social behavior deficits and modifies the transcription of inhibitory/excitatory genes in the frontal cortex of an autism model.

The core behavioral symptoms of Autism Spectrum Disorders (ASD) include dysregulation of social communication and the presence of repetitive behaviors. However, there is no pharmacological agent that is currently used to target these core symptoms. Epigenetic dysregulation has been implicated in the etiology of ASD, and may present a pharmacological target.

DNA methylation analysis of the autistic brain reveals multiple dysregulated biological pathways.

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions characterized by dysfunction in social interaction, communication and stereotypic behavior. Genetic and environmental factors have been implicated in the development of ASD, but the molecular mechanisms underlying their interaction are not clear. Epigenetic modifications have been suggested as molecular mechanism that can mediate the interaction between the environment and the genome to produce adaptive or maladaptive behaviors.

A triple urocortin knockout mouse model reveals an essential role for urocortins in stress recovery.

Responding to stressful events requires numerous adaptive actions involving integrated changes in the central nervous and neuroendocrine systems. Numerous studies have implicated dysregulation of stress-response mechanisms in the etiology of stress-induced psychopathophysiologies. The urocortin neuropeptides are members of the corticotropin-releasing factor family and are associated with the central stress response.

Prolonged and site-specific over-expression of corticotropin-releasing factor reveals differential roles for extended amygdala nuclei in emotional regulation.

Corticotropin-releasing factor (CRF) has a key role in the central stress response, and altered levels of this neuropeptide are linked to stress-related psychopathologies such as anxiety and depression. These disorders are associated with the inability to properly regulate stress response, specifically following exposure to prolonged stressful stimuli. Therefore, the current study assessed the effects of prolonged and site-specific over-expression of CRF, which mimics the state of chronic production, in extended amygdala nuclei that are known to be involved in mediating anxiety-like states.

Amelioration of brain pathology and behavioral dysfunction in mice with lupus following treatment with a tolerogenic peptide.

Objective: Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is manifested by neurologic deficits and psychiatric disorders. The aim of this study was to examine SLE-associated CNS pathology in lupus-prone (NZBxNZW)F1 (NZB/NZW) mice, and to evaluate the ameliorating effects of treatment with a tolerogenic peptide, hCDR1 (human first complementarity-determining region), on these manifestations.

Methods: Histopathologic analyses of brains from lupus-prone NZB/NZW mice treated with vehicle, hCDR1, or a control scrambled peptide were performed.

Urocortin-1 and -2 double-deficient mice show robust anxiolytic phenotype and modified serotonergic activity in anxiety circuits.

The urocortin (Ucn) family of neuropeptides is suggested to be involved in homeostatic coping mechanisms of the central stress response through the activation of corticotropin-releasing factor receptor type 2 (CRFR2). The neuropeptides, Ucn1 and Ucn2, serve as endogenous ligands for the CRFR2, which is highly expressed by the dorsal raphe serotonergic neurons and is suggested to be involved in regulating major component of the central stress response. Here, we describe genetically modified mice in which both Ucn1 and Ucn2 are developmentally deleted.