Probiotic treatment with subsp. LKM512 + arginine improves cognitive flexibility in middle-aged mice.

Cognitive flexibility, the ability of adapting to an ever-changing environment, declines with aging and impaired in early stages of dementia. Although recent studies have indicated there is a relationship between the intestinal microbiota and cognitive function, few studies have shown relationships between intestinal microbiota and cognitive flexibility because of limited behavioural tasks in mice. We recently established a novel cognitive flexibility task for mice using a touchscreen operant apparatus and found that probiotic treatment with a mixture of subsp.

2-Chloro-3,7,8-tribromodibenzofuran as a new environmental pollutant inducing atypical ultrasonic vocalization in infant mice.

Epidemiological and experimental studies indicate that maternal exposure to environmental pollutants impairs the cognitive and motor functions of offspring in humans and laboratory animals. Infant ultrasonic vocalizations (USVs), the communicative behavior of pups toward caregivers, are impaired in rodent models of neurodevelopmental disorders, suggesting a useful method to evaluate the developmental neurotoxicity of environmental pollutants. Therefore, we investigated USVs emitted by mouse pups of dams exposed to 2-chloro-3,7,8-tribromodibenzofuran (TeXDF) and 1,2,3,7,8-pentabromodibenzofuran (PeBDF), which are detected in the actual environment.

Purposive decision-making task in mice using touchscreen operant apparatus.

Purposive decision-making, based on sensory input and memory, is a component of executive functioning. Evaluating executive functioning is crucial for understanding neuropsychiatric disorders and brain injuries. However, there's a lack of mouse tests for this purpose.

subsp. and arginine mixture intake improves cognitive flexibility in mice.

The relationship between intestinal microbiota and cognitive function has been investigated as one of the major topics within the intestinal microbiota-gut-brain axis. Although an increasing number of studies have demonstrated an improvement in learning and memory when using probiotics or prebiotics, to date, there are no studies that target the cognitive flexibility observed in the early stages of several neuropsychiatric diseases, including dementia. We have recently developed a novel behavioral task using the touchscreen operant system to assess cognitive flexibility.

Impact of Intestinal Microbiota on Cognitive Flexibility by a Novel Touch Screen Operant System Task in Mice.

Cognitive flexibility is the ability to rapidly adapt to a constantly changing environment. It is impaired by aging as well as in various neurological diseases, including dementia and mild cognitive impairment. In rodents, although many behavioral test protocols have been reported to assess learning and memory dysfunction, few protocols address cognitive flexibility.

Distinctive Regulation of Emotional Behaviors and Fear-Related Gene Expression Responses in Two Extended Amygdala Subnuclei With Similar Molecular Profiles.

The central nucleus of the amygdala (CeA) and the lateral division of the bed nucleus of the stria terminalis (BNST) are the two major nuclei of the central extended amygdala that plays essential roles in threat processing, responsible for emotional states such as fear and anxiety. While some studies suggested functional differences between these nuclei, others showed anatomical and neurochemical similarities. Despite their complex subnuclear organization, subnuclei-specific functional impact on behavior and their underlying molecular profiles remain obscure.

Liver-specific decrease in Tff3 gene expression in infant mice perinatally exposed to 2,3,7,8-tetrabromodibenzofuran or 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/DFs) are byproducts of brominated flame retardants and can cause adverse health effects. Although exposure to polychlorinated (PC) DD/DFs induces toxic effects, including liver injury and neurobehavioral disorder, little is known about toxicities associated with PBDD/DF exposure. Thus, we examined effects of perinatal exposure to brominated congener on the infant mouse.

A mouse model of Timothy syndrome exhibits altered social competitive dominance and inhibitory neuron development.

Multiple genetic factors related to autism spectrum disorder (ASD) have been identified, but the biological mechanisms remain obscure. Timothy syndrome (TS), associated with syndromic ASD, is caused by a gain-of-function mutation, G406R, in the pore-forming subunit of L-type Ca channels, Ca 1.2.

Multiple animal positioning system shows that socially-reared mice influence the social proximity of isolation-reared cagemates.

Social relationships are a key determinant of social behaviour, and disruption of social behaviour is a major symptom of several psychiatric disorders. However, few studies have analysed social relationships among multiple individuals in a group or how social relationships within a group influence the behaviour of members with impaired socialisation. Here, we developed a video-analysis-based system, the Multiple-Animal Positioning System (MAPS), to automatically and separately analyse the social behaviour of multiple individuals in group housing.

Neurochemical evidence for differential effects of acute and repeated oxytocin administration.

A discrepancy in oxytocin's behavioral effects between acute and repeated administrations indicates distinct underlying neurobiological mechanisms. The current study employed a combination of human clinical trial and animal study to compare neurochemical changes induced by acute and repeated oxytocin administrations. Human study analyzed medial prefrontal metabolite levels by using H-magnetic resonance spectroscopy, a secondary outcome in our randomized, double-blind, placebo-controlled crossover trial of 6 weeks intranasal administrations of oxytocin (48 IU/day) and placebo within-subject design in 17 psychotropic-free high-functioning men with autism spectrum disorder.

[Genetic and Environmental Factors in Childhood Affecting High Brain Function].

The brain and mind are not only determined genetically but are also nurtured by environmental stimuli in early life. However, the relationship between early life environment and phenotypes in adulthood remains elusive. Using the IntelliCage-based competition task for group-housed mice, we previously found that maternal exposure to a low dose of an environmental pollutant, dioxin, resulted in abnormal social behavior, that is, low competitive dominance, which is defined by decreased occupancy of limited resource sites under highly competitive circumstances.

Impaired dendritic growth and positioning of cortical pyramidal neurons by activation of aryl hydrocarbon receptor signaling in the developing mouse.

The basic helix-loop-helix (bHLH) transcription factors exert multiple functions in mammalian cerebral cortex development. The aryl hydrocarbon receptor (AhR), a member of the bHLH-Per-Arnt-Sim subfamily, is a ligand-activated transcription factor reported to regulate nervous system development in both invertebrates and vertebrates, but the functions that AhR signaling pathway may have for mammalian cerebral cortex development remains elusive. Although the endogenous ligand involved in brain developmental process has not been identified, the environmental pollutant dioxin potently binds AhR and induces abnormalities in higher brain function of laboratory animals.

Association of impaired neuronal migration with cognitive deficits in extremely preterm infants.

Many extremely preterm infants (born before 28 gestational weeks [GWs]) develop cognitive impairment in later life, although the underlying pathogenesis is not yet completely understood. Our examinations of the developing human neocortex confirmed that neuronal migration continues beyond 23 GWs, the gestational week at which extremely preterm infants have live births. We observed larger numbers of ectopic neurons in the white matter of the neocortex in human extremely preterm infants with brain injury and hypothesized that altered neuronal migration may be associated with cognitive impairment in later life.

Excessive activation of AhR signaling disrupts neuronal migration in the hippocampal CA1 region in the developing mouse.

The aryl hydrocarbon receptor (AhR) avidly binds dioxin, a ubiquitous environmental contaminant. Disruption of downstream AhR signaling has been reported to alter neuronal development, and rodent offspring exposed to dioxin during gestation and lactation showed abnormalities in learning and memory, emotion, and social behavior. However, the mechanism behind the disrupted AhR signaling and developmental neurotoxicity induced by xenobiotic ligands remains elusive.

In utero and lactational dioxin exposure induces Sema3b and Sema3g gene expression in the developing mouse brain.

In the developing mammalian brain, neural network formation is regulated by complex signaling cascades. In utero and lactational dioxin exposure is known to induce higher brain function abnormalities and dendritic growth disruption in rodents. However, it is unclear whether perinatal dioxin exposure affects the expression of genes involved in neural network formation.

Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice.

Exposure to arsenic from well water in developing countries is suspected to cause developmental neurotoxicity. Although, it has been demonstrated that exposure to sodium arsenite (NaAsO2) suppresses neurite outgrowth of cortical neurons in vitro, it is largely unknown how developmental exposure to NaAsO2 impairs higher brain function and affects cortical histology. Here, we investigated the effect of prenatal NaAsO2 exposure on the behavior of mice in adulthood, and evaluated histological changes in the prelimbic cortex (PrL), which is a part of the medial prefrontal cortex that is critically involved in cognition.

In Utero Bisphenol A Exposure Induces Abnormal Neuronal Migration in the Cerebral Cortex of Mice.

Bisphenol A (BPA) has been known to have endocrine-disrupting activity to induce reproductive and behavioral abnormalities in offspring of laboratory animal species. However, morphological basis of this abnormality during brain development is largely unknown. Cerebral cortex plays a crucial role in higher brain function, and its precisely laminated structure is formed by neuronal migration.

Developmental origin of abnormal dendritic growth in the mouse brain induced by in utero disruption of aryl hydrocarbon receptor signaling.

Increased prevalence of mental disorders cannot be solely attributed to genetic factors and is considered at least partly attributable to chemical exposure. Among various environmental chemicals, in utero and lactational dioxin exposure has been extensively studied and is known to induce higher brain function abnormalities in both humans and laboratory animals. However, how the perinatal dioxin exposure affects neuromorphological alterations has remained largely unknown.

Neuronal Heterotopias Affect the Activities of Distant Brain Areas and Lead to Behavioral Deficits.

Neuronal heterotopia refers to brain malformations resulting from deficits of neuronal migration. Individuals with heterotopias show a high incidence of neurological deficits, such as epilepsy. More recently, it has come to be recognized that focal heterotopias may also show a range of psychiatric problems, including cognitive and behavioral impairments.

Application of NeuroTrace staining in the fresh frozen brain samples to laser microdissection combined with quantitative RT-PCR analysis.

Background: The heterogeneity of the brain requires appropriate molecular biological approaches to account for its morphological complexity. Laser-assisted microdissection followed by transcript profiling by quantitative determination has been reported to be an optimal methodology. Nevertheless, not all brain regions can be identified easily without staining, restricting the accuracy and efficiency in sampling.

Developmental changes in the neural responses to own and unfamiliar mother's smiling face throughout puberty.

An attachment relationship between boys and their mother is important for subsequent development of the ability to sustain peer relationships. Affective responses to attachment figure, especially mother, is supposed to change drastically during puberty. To elucidate the neural correlates underlying this behavioral change, we compared the neural response of boys at three different developmental stages throughout puberty to visual image of their own mothers.

[Development of Higher Brain Function Tests in Rodents and Its Application to Neurotoxicity Assessment of Environmental Chemicals].

The brain during developmental period is thought to be highly sensitive to environmental insults including exposure to chemicals. However, it has been extremely difficult to detect and assess the features and degree of adversity particularly at low exposure levels. I describe here the effects of maternal exposure to dioxin on higher brain functions later in life, which we detected using our originally developed behavioral tests for quantifying higher brain functions in rodents.

Environmental insults in early life and submissiveness later in life in mouse models.

Dominant and subordinate dispositions are not only determined genetically but also nurtured by environmental stimuli during neuroendocrine development. However, the relationship between early life environment and dominance behavior remains elusive. Using the IntelliCage-based competition task for group-housed mice, we have previously described two cases in which environmental insults during the developmental period altered the outcome of dominance behavior later in life.

Prenatal exposure to bisphenol A impacts neuronal morphology in the hippocampal CA1 region in developing and aged mice.

Bisphenol A (BPA), a widely used raw component of polycarbonate plastics and epoxy resins, has been reported to induce developmental neurotoxicity in offspring born to dams exposed to low doses of BPA; however, the toxicity mechanism remains elusive. To study the effects of in utero BPA exposure on neuronal morphology, we studied spine density and dendritic growth in the hippocampal CA1 of aged mice and developing mice prenatally exposed to low doses of BPA. Pregnant mice were orally administered BPA at a low dose of 0, 40, or 400 μg/kg body weight/day on gestational days 8.

Early deprivation induces competitive subordinance in C57BL/6 male mice.

Rodent models have been widely used to investigate the impact of early life stress on adult health and behavior. However, the social dimension has rarely been incorporated into the analysis due to methodological limitations. This study characterized the effects of neonatal social isolation (early deprivation, ED) on adult C57BL/6 mouse behavior in a social context using our recently developed behavioral test protocols for group-housed mice.