Publications by authors named "Michihiro Toritsuka"

Dendritic spine abnormalities are believed to be one of the critical etiologies of autism spectrum disorder (ASD). Over the past decade, the importance of microglia in brain development, particularly in synaptic elimination, has become evident. Thus, microglial abnormalities may lead to synaptic dysfunction, which may underlie the pathogenesis of ASD.

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Individuals with autism spectrum disorder (ASD) are more likely to experience adverse childhood experiences (ACEs) compared with typically developing (TD) individuals, which predisposes them to an elevated risk of mental health issues. This review elucidates the profound impact of ACEs on individuals with ASD by synthesizing findings from a plethora of epidemiologic and biological studies, encompassing genetics, epigenetics, and neuroimaging. Despite the limited number of studies explicitly focusing on this intersection, the extant literature consistently demonstrates that ASD individuals are disproportionately affected by ACEs, leading to significant deterioration in mental health and brain function.

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Aim: Adverse childhood experiences are potentially traumatic events with long-lasting effects on the health and well-being of patients with autism spectrum disorder (ASD). It is important to clarify which types of long-lasting autism-related symptoms are influenced by childhood experiences to design future intervention studies. However, few studies have examined the association between childhood experiences and autistic symptoms in large samples of adults with ASD and individuals with typical development (TD).

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  • The study explores how social isolation during critical development stages affects behavior and neuronal activity, focusing on the expression of specific proteins in the prefrontal cortex (PFC) of mice.
  • Researchers compared socially isolated mice with those kept in groups, observing changes in neuronal firing patterns and social behavior.
  • Results indicated that isolated mice struggled with social memory, and decreased NARP expression was found in humans with autism compared to typically developing individuals, suggesting a link between social isolation and behavioral outcomes.
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Background: A growing body of evidence suggests that immune dysfunction and inflammation in the peripheral tissues as well as the central nervous system are associated with the neurodevelopmental deficits observed in autism spectrum disorder (ASD). Elevated expression of pro-inflammatory cytokines in the plasma, serum, and peripheral blood mononuclear cells of ASD has been reported. These cytokine expression levels are associated with the severity of behavioral impairments and symptoms in ASD.

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  • * Social isolation led to increased BDNF in microglia and decreased sociability in adulthood, while manipulating BDNF levels at different juvenile stages had varying impacts on social behavior and neural function in the mPFC.
  • * The study also found a correlation between adverse childhood experiences and BDNF expression in human macrophages, suggesting the importance of BDNF in shaping social behaviors not only in mice but potentially also in humans.
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  • Microglia and brain-derived neurotrophic factor (BDNF) play a crucial role in the development of social behaviors in mice, particularly during the critical juvenile period.
  • Social isolation in young mice led to increased microglia and reduced sociability in adulthood, while manipulating BDNF levels in transgenic mice showed that prolonged overexpression of microglia BDNF negatively impacted sociability and mPFC function.
  • Findings suggest that microglia BDNF is vital for juvenile social development, and human studies indicate that adverse childhood experiences may influence BDNF expression in macrophages, hinting at a potential link between early experiences and sociability.
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Schizophrenia is a major psychiatric disorder, but the molecular mechanisms leading to its initiation or progression remain unclear. To elucidate the pathophysiology of schizophrenia, we used an in vitro neuronal cell culture model involving human induced pluripotent stem cells (hiPSCs) derived from a monozygotic-twin discordant schizophrenia pair. The cultured neurons differentiated from hiPSCs were composed of a mixture of glutamatergic excitatory neurons and gamma aminobutyric acid (GABA)ergic inhibitory neurons.

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  • * Results show that TNF-α levels are significantly higher in M1 macrophages from ASD patients compared to TD individuals, indicating a potential diagnostic marker, while no differences were found in monocytes.
  • * The findings suggest that examining TNF-α expression in macrophages could enhance understanding of the underlying biology of ASD and aid in developing diagnostic biomarkers for high-functioning adults with ASD.
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Background: Transurethral resection of bladder tumor (TURBT) is an essential procedure both for the treatment and staging of bladder cancer, particularly non-muscle invasive bladder cancer (NMIBC). The dissemination of cancer cells during resection and the consequent seeding into the bladder mucosa is the main cause of post-TURBT intravesical recurrence. Although the tumor dissemination is inevitable during conventional TURBT (cTURBT), this drawback can be overcome by tumor resection in one piece with intact surrounding normal tissues, referred to as en bloc resection.

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Background: It has been reported that delirium causes various problems. Many researchers have reported the risk factors associated with the onset of delirium; however, there are few reports focused on persistent delirium. This study aimed to identify the risk factors associated with persistent delirium.

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Background: Radiotherapy is one of the most frequently selected treatment options for patients with prostate cancer. However, adverse effects related to the irradiated surrounding normal organs are significant clinical concerns. Specifically, genitourinary and gastrointestinal toxicities can lead to a dramatically reduced quality of life.

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Despite advances and refinements in surgery and perioperative chemotherapy, there are still unmet medical needs with respect to radical cystectomy for muscle-invasive bladder cancer (MIBC). We investigated the potential benefit of supplementary granulocyte macrophage colony-stimulating factor (GM-CSF) to chemoimmunotherapy with programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis blockade and standard neoadjuvant chemotherapy in bladder cancer. We inoculated 2 × 10 MBT2 cells s.

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The gut hormone ghrelin has been implicated in a variety of functional roles in the central nervous system through the brain-gut axis, one of which is an anti-inflammatory effect. An aberrant brain-gut axis producing immune dysfunction has been implicated in the pathobiology of autism spectrum disorder (ASD), and elevated expression of inflammatory markers has been shown in blood and brain tissue from subjects with ASD. We hypothesized that ghrelin may mitigate this effect.

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Lymphoblastoid cell lines (LCLs) are nearly immortalized B lymphocytes that are used as long-lasting supply of human cells for studies on gene expression analyses. However, studies on the stability of the cellular features of LCLs are scarce. To address this issue, we measured gene expression in LCLs with different passage numbers and observed that gene expression substantially changed within 10 passages.

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Background: Schizophrenia (SZ) and bipolar disorder (BD) are characterized by different clinical symptoms, and have previously been considered as categorically separate. However, several lines of evidence controversially suggest that these two disorders may run on a continuum. While it is therefore important to evaluate the subtle differences between SZ and BD, few studies have investigated the difference of brain functioning between the two by focusing on the common symptoms of cognitive functioning and impulsivity, rather than positive/negative and mood symptoms.

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction, poor communication skills, and repetitive/restrictive behaviors. Recent studies have indicated that early rehabilitative intervention can alleviate the symptoms of individuals with ASD. However, it remains unknown whether rehabilitative intervention can restore brain structures such as myelin, which generally shows abnormalities in individuals with ASD.

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Social isolation is an important factor in the development of psychiatric disorders. It is necessary to develop an effective psychological treatment, such as cognitive rehabilitation, for children who have already suffered from social isolation, such as neglect and social rejection. We used socially isolated mice to validate whether elaborate re-socialization after juvenile social isolation can restore hypomyelination in the medial prefrontal cortex (mPFC) and the attendant functions manifested in socially isolated mice.

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Current knowledge of the molecular mechanism driving tumor budding is limited. Here, we focused on elucidating the detailed mechanism underlying tumor budding in urothelial cancer of the bladder. Invasive urothelial cancer was pathologically classified into three groups as follows: nodular, trabecular, and infiltrative (tumor budding).

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Juvenile social experience is crucial for the functional development of forebrain regions, especially the prefrontal cortex (PFC). We previously reported that social isolation for 2 weeks after weaning induces prefrontal cortex dysfunction and hypomyelination. However, the effect of social isolation on physiological properties of PFC neuronal circuit remained unknown.

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Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorder (ASD).

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Autism spectrum disorder is a neurodevelopmental disorder characterized by impaired social interaction, poor communication skills, and repetitive/restrictive behaviors. Elevated blood levels of pro-inflammatory cytokines have been reported in subjects with autism spectrum disorder. On the other hand, early childhood adverse experience also increases blood levels of these cytokines.

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Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are reported to be associated with poor prognosis, depending on their pro-tumoral roles. Current knowledge of TAMs and CAFs in the tumor microenvironment of urothelial cancer of the bladder (UCB) is limited. Therefore, we investigated the paracrine effect induced by TAMs and CAFs in the tumor microenvironment of human UCB.

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Recent studies have revealed that social experience affects myelination. These findings have important implications for disorders that feature abnormal myelination, such as multiple sclerosis (MS), as previous studies have shown that psychosocial stress exacerbates the pathobiology of MS. However, most studies have focused on psychosocial stress during the demyelination phase of MS and have not investigated the effects of social experience on remyelination.

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