Publications by authors named "Keiko Nakagaki"

In autism spectrum disorder (ASD), atypical sensory experiences are often associated with irregularities in predictive coding, which proposes that the brain creates hierarchical sensory models via a bidirectional process of predictions and prediction errors. However, it remains unclear how these irregularities manifest across different functional hierarchies in the brain. To address this, we study a marmoset model of ASD induced by valproic acid (VPA) treatment.

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Alterations in the experience-dependent and autonomous elaboration of neural circuits are assumed to underlie autism spectrum disorder (ASD), though it is unclear what synaptic traits are responsible. Here, utilizing a valproic acid-induced ASD marmoset model, which shares common molecular features with idiopathic ASD, we investigate changes in the structural dynamics of tuft dendrites of upper-layer pyramidal neurons and adjacent axons in the dorsomedial prefrontal cortex through two-photon microscopy. In model marmosets, dendritic spine turnover is upregulated, and spines are generated in clusters and survived more often than in control marmosets.

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Individuals with autism spectrum disorder (ASD) are exposed to a variety of stressors owing to their behavioral traits. Cortisol is a hormone typically associated with stress, and its concentration and response to stress are higher in individuals with ASD than in controls. The mechanisms underlying cortisol dysregulation in ASD have been explored in rodents.

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Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social and communication impairments and restricted and repetitive behavior. Although there is currently no established cure for ASD, early interventions for deficits of attention to other individuals are expected to reduce the progression of ASD symptoms in later life. To confirm this hypothesis and improve early therapeutic interventions, it is desirable to develop an animal model of ASD in which social attention is impaired in childhood and ASD-like social behavior is observed in adulthood.

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Autism spectrum disorder (ASD) is a multifactorial disorder with characteristic synaptic and gene expression changes. Early intervention during childhood is thought to benefit prognosis. Here, we examined the changes in cortical synaptogenesis, synaptic function, and gene expression from birth to the juvenile stage in a marmoset model of ASD induced by valproic acid (VPA) treatment.

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Autism spectrum disorder (ASD) is one of the most widespread neurodevelopmental disorders, characterized by impairment in social interactions, and restricted stereotyped behaviors. Using immunohistochemistry and positron emission tomography (PET), several studies have provided evidence of the existence of activated microglia in ASD patients. Recently, we developed an animal model of ASD using the new world monkey common marmoset () and demonstrated ASD-like social impairment after the administration of valproic acid (VPA).

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In autism spectrum disorder (ASD), disrupted functional and structural connectivity in the social brain has been suggested as the core biological mechanism underlying the social recognition deficits of this neurodevelopmental disorder. In this study, we aimed to identify genetic and neurostructural abnormalities at birth in a non-human primate model of ASD, the common marmoset with maternal exposure to valproic acid (VPA), which has been reported to display social recognition deficit in adulthood. Using a comprehensive gene expression analysis, we found that 20 genes were significantly downregulated in VPA-exposed neonates.

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Humans and various nonhuman primates respond negatively to inequity not in their favor (i.e., inequity aversion), when inequity between two individuals is introduced.

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Autism is characterized by deficits in social interaction and social recognition. Although animal models of autism have demonstrated that model animals engage less in social interaction or attend less to conspecifics than control animals, no animal model has yet replicated the deficit in recognition of complex social interaction as is seen in humans with autism. Here, we show that marmosets discriminated between human actors who reciprocated in social exchanges and those who did not; however, marmosets with foetal exposure to valproic acid (VPA marmosets) did not.

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Although human coronavirus (HCoV)-NL63 was once considered a possible causative agent of Kawasaki disease based on RT-PCR analyses, subsequent studies could not confirm the result. In this study, this possibility was explored using serological tests. To evaluate the role of HCoV infection in patients with Kawasaki disease, immunofluorescence assays and virus neutralizing tests were performed.

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The synapse number and the related dendritic spine number in the cerebral cortex of primates shows a rapid increase after birth. Depending on the brain region and species, the number of synapses reaches a peak before adulthood, and pruning takes place after this peak (overshoot-type synaptic formation). Human mental disorders, such as autism and schizophrenia, are hypothesized to be a result of either too weak or excessive pruning after the peak is reached.

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This is the second report of a series paper, which reports molecular mechanisms underlying the occurrence of pruning spine phase after rapid spinogenesis phase in neonates and young infant in the primate brain. We performed microarray analysis between the peak of spine numbers [postnatal 3 months (M)] and spine pruning (postnatal 6M) in prefrontal, inferior temporal, and primary visual cortices of the common marmoset (Callithrix jacchus). The pruning phase is not clearly defined in rodents but is in primates including the marmoset.

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Although most inbred mouse strains are highly susceptible to mouse hepatitis virus (MHV) infection, the inbred SJL line of mice is highly resistant to its infection. The principal receptor for MHV is murine CEACAM1 (mCEACAM1). Susceptible strains of mice are homozygous for the 1a allele of mCeacam1, while SJL mice are homozygous for the 1b allele.

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To facilitate common marmoset brain research, we produced a DNA microarray with 7557 probe sets derived from the common marmoset brain. Gene expression profiles in the frontal lobe, hippocampus, cerebellum and amygdaloid nucleus were then analyzed and the top 100 probe sets expressed in each structure were compared. The three lists for the frontal lobe, hippocampus and amygdaloid nucleus were very similar but the probe sets for the cerebellum demonstrated specific differences.

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SARS-CoV grows in a variety of tissues that express its receptor, although the mechanism for high replication in the lungs and severe respiratory illness is not well understood. We recently showed that elastase enhances SARS-CoV infection in cultured cells, which suggests that SARS development may be due to elastase-mediated, enhanced SARS-CoV infection in the lungs. To explore this possibility, we examined whether co-infection of mice with SARS-CoV and Pp, a low-pathogenic bacterium which elicits elastase production in the lungs, induces exacerbation of pneumonia.

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Although neurovirulent mouse hepatitis virus (MHV) strain JHMV multiplies in a variety of brain cells, expression of its receptor carcinoembryonic antigen cell adhesion molecule 1 (CEACAM 1) (MHVR) is restricted only in microglia. The present study was undertaken to clarify the mechanism of an extensive JHMV infection in the brain by using neural cells isolated from mouse brain. In contrast to wild-type (wt) JHMV, a soluble-receptor-resistant mutant (srr7) infects and spreads solely in an MHVR-dependent fashion (F.

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The mouse hepatitis virus (MHV) receptor (MHVR), CEACAM1, has two different functions for MHV entry into cells: binding to MHV spike protein (S protein) and activation of the S protein to execute virus-cell membrane fusion, the latter of which is accompanied by conformational changes of the S protein. The MHVR comprising the N-terminal and fourth domains [R1(1,4)] displays these two activities, and the N domain is thought to be critical for binding to MHV. In this study, we have addressed whether or not the N domain alone is sufficient for these activities.

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