Loss of Orai2-Mediated Capacitative Ca Entry Is Neuroprotective in Acute Ischemic Stroke.

Background and Purpose- Ischemic stroke is one of the leading causes of disability and death. The principal goal of acute stroke treatment is the recanalization of the occluded cerebral arteries, which is, however, only effective in a very narrow time window. Therefore, neuroprotective treatments that can be combined with recanalization strategies are needed.

Limited effects of early life manipulations on sex-specific gene expression and behavior in adulthood.

Exposure to childhood adversity is associated with increased vulnerability to stress-related disorders in adulthood which has been replicated in rodent stress models, whereas environmental enrichment has been suggested to have beneficial effects. However, the exact neurobiological mechanisms underlying these environment influences on adult brain and behavior are not well understood. Therefore, we investigated the long-term effects of maternal separation (MS) or environmental enrichment (EE) in male and female CD1 mice.

Prenatal and postnatal experiences associated with epigenetic changes in the adult mouse brain.

To analyze the influences of early-life history on the brain epigenome, the offspring of mouse dams kept in an enriched or standard environment were exposed postnatally to enriched, standard, or adverse conditions. The methylation patterns of 7 candidate genes (9 loci) involved in developmental programming of stress vulnerability/resilience and psychiatric disease were analyzed in 6 brain regions of adult male and female mice. Exposure to an enriched prenatal environment was associated with widespread epigenetic changes (all of small effect size), affecting 29 of 324 (9%) gene/region-specific methylation patterns.

The regulation of tetraspanin 8 gene expression-A potential new mechanism in the pathogenesis of bipolar disorder.

In a previous study, we identified the single nucleotide polymorphism (SNP) rs4500567, located in the upstream region of tetraspanin 8 (TSPAN8), to be associated with bipolar disorder (BD). Due to its proximal position, the SNP might have an impact on promoter activity, thus on TSPAN8 gene expression. We investigated the impact of rs4500567 on TSPAN8 expression in vitro with luciferase-based promoter assays in human embryonic kidney (HEK293) and neuroblastoma cells (SH-SY5Y), and its effect on expression of downstream associated genes by microarray-based transcriptome analyses.

Interaction of NOS1AP with the NOS-I PDZ domain: Implications for schizophrenia-related alterations in dendritic morphology.

Schizophrenia involves morphological brain changes, including changes in synaptic plasticity and altered dendritic development. Amongst the most promising candidate molecules for schizophrenia are neuronal nitric oxide (NO) synthase (NOS-I, also known as nNOS) and its adapter protein NOS1AP (previously named CAPON). However, the precise molecular mechanisms by which NOS-I and NOS1AP affect disease pathology remain to be resolved.

Aggression in non-human vertebrates: Genetic mechanisms and molecular pathways.

Aggression is an adaptive behavioral trait that is important for the establishment of social hierarchies and competition for mating partners, food, and territories. While a certain level of aggression can be beneficial for the survival of an individual or species, abnormal aggression levels can be detrimental. Abnormal aggression is commonly found in human patients with psychiatric disorders.

On the role of NOS1 ex1f-VNTR in ADHD-allelic, subgroup, and meta-analysis.

Attention deficit/ hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder featuring complex genetics with common and rare variants contributing to disease risk. In a high proportion of cases, ADHD does not remit during adolescence but persists into adulthood. Several studies suggest that NOS1, encoding nitric oxide synthase I, producing the gaseous neurotransmitter NO, is a candidate gene for (adult) ADHD.

Interaction of brain 5-HT synthesis deficiency, chronic stress and sex differentially impact emotional behavior in Tph2 knockout mice.

Rationale: While brain serotonin (5-HT) function is implicated in gene-by-environment interaction (GxE) impacting the vulnerability-resilience continuum in neuropsychiatric disorders, it remains elusive how the interplay of altered 5-HT synthesis and environmental stressors is linked to failure in emotion regulation.

Objective: Here, we investigated the effect of constitutively impaired 5-HT synthesis on behavioral and neuroendocrine responses to unpredictable chronic mild stress (CMS) using a mouse model of brain 5-HT deficiency resulting from targeted inactivation of the tryptophan hydroxylase-2 (Tph2) gene.

Results: Locomotor activity and anxiety- and depression-like behavior as well as conditioned fear responses were differentially affected by Tph2 genotype, sex, and CMS.

Experimental heart failure causes depression-like behavior together with differential regulation of inflammatory and structural genes in the brain.

Background: Depression and anxiety are common and independent outcome predictors in patients with chronic heart failure (CHF). However, it is unclear whether CHF causes depression. Thus, we investigated whether mice develop anxiety- and depression-like behavior after induction of ischemic CHF by myocardial infarction (MI).

The COGITAT holeboard system as a valuable tool to assess learning, memory and activity in mice.

The comprehensive and stress-free assessment of various aspects of learning and memory is a prerequisite to evaluate mouse models for neuropsychiatric disorders such as Alzheimer's disease or attention deficit/hyperactivity disorder (ADHD). COGITAT is an automated holeboard system allowing simultaneous assessment of spatial working and reference-memory performance which we have adapted in this study to enable its usage with mice. The holeboard apparatus consists of an open-field chamber with a 25-hole floor insert, each hole being monitored by infrared light beams, located on three different levels, allowing the distinction between visits of holes, i.

Gene-environment interaction influences anxiety-like behavior in ethologically based mouse models.

Ethologically based animal models are widely used; however, results from different laboratories vary significantly which may partly be due to the lack of standardization. Here, we examined the effects of circadian rhythm, lighting condition and mouse strain (BALB/c and C57BL/6, known to differ in measures of avoidance and risk assessment behavior) on two well established behavioral tests in mice: the Elevated Plus Maze (EPM) and the Open Field (OF). Parameters from both paradigms are commonly used as indices of anxiety-like behavior.