Institute for Comprehensive Medical Science
Profile Information
- Affiliation
- Division of Systems Medical Sicence, Center for Medical Science, Fujita Health University
- Degree
- 博士（行動科学）(Mar, 2007, （筑波大学）)
- Researcher number
- 00466278
- ORCID ID
https://orcid.org/0000-0003-4843-6949- J-GLOBAL ID
- 201101086288639254
- researchmap Member ID
- B000001820
- External link
遺伝子改変マウスの行動解析を基点として精神疾患モデルマウスを確立し、精神疾患の脳内機序の解明を試みています。
Research Interests
16Research Areas
3Research History
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Apr, 2024 - Present
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Apr, 2022 - Mar, 2024
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Oct, 2018 - Mar, 2022
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Apr, 2013 - Sep, 2018
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Apr, 2010 - Mar, 2013
Education
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Apr, 2002 - Mar, 2007
Awards
5-
Sep, 2018
Papers
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Molecular neurobiology, 62(9) 12078-12093, Sep, 2025Hyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia (CHN) may induce neurological manifestations, including psychological symptoms. However, the specific psychological symptoms induced by CHN, the mechanisms underlying these symptoms, and their potential reversibility remain unclear. Therefore, this study aimed to determine whether monoaminergic neurotransmission is associated with innate anxiety-like behaviors potentiated by CHN in a mouse model of CHN secondary to the syndrome of inappropriate antidiuresis. In the present study, using a mouse model of the syndrome of inappropriate antidiuresis presenting with CHN, we showed that the sustained reduction of serum sodium ion concentrations potentiated innate anxiety-like behaviors in the light/dark transition and open field tests. We also found that serotonin and dopamine levels in the amygdala were significantly lower in mice with CHN than in controls. Additionally, phosphorylation of extracellular signal-regulated kinase (ERK) in the amygdala was significantly reduced in mice with CHN. Notably, after correcting for CHN, the increased innate anxiety-like behaviors, decreased serotonin and dopamine levels, and reduced phosphorylation of ERK in the amygdala were normalized. These findings further underscore the importance of treating CHN and highlight potential therapeutic strategies for alleviating anxiety in patients with CHN, which will improve their quality of life.
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The international journal of neuropsychopharmacology, Aug 23, 2025BACKGROUND: The hippocampal dentate gyrus (DG) is a critical region that contributes to recent and remote memory. Granule cells within this region, in which adult neurogenesis occurs, undergo dynamic and reversible maturation via genetic and environmental factors during adulthood. A pseudo-immature state of DG granule cells, called immature DG (iDG), has been observed in the adult mice of certain mutant strains, which are considered animal models of neuropsychiatric and neurodegenerative disorders, such as intellectual disability, schizophrenia, autism, and Alzheimer's disease. However, the association between the iDG phenotype and recent and remote memories in the mouse models remains unclear. METHODS: We assessed spatial memory in the Barnes circular maze task in five mutant mouse models of the disorders with the iDG phenotype, including Camk2a heterozygous knockout (HET KO), forebrain-specific Calcineurin conditional KO (cKO), Neurogranin KO, and Hivep2 (Schnurri-2) KO, and hAPP-J20 transgenic mice. RESULTS: Camk2a HET KO mice and J20 mice spent less time around the target than their wild-type control mice in the memory retention tests one day and four weeks after the last training session. Calcineurin cKO, Neurogranin KO, and Schnurri-2 KO mice showed no significant differences in the time spent around the target from wild-type mice in the retention test 1 day after the training session, but those mutants spent less time around the target than their wild-type mice in the retest conducted four weeks later. CONCLUSIONS: These results indicated that mouse models of neuropsychiatric and neurodegenerative disorders exhibiting the iDG phenotype demonstrate a common behavioral characteristic of remote spatial memory deficits, suggesting the potential involvement of the pseudo-immature state of DG granule cells in remote memory dysfunction.
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Molecular brain, 17(1) 79-79, Nov 7, 2024Chronic exposure to glucocorticoids in response to long-term stress is thought to be a risk factor for major depression. Depression is associated with disturbances in the gut microbiota composition and peripheral and central energy metabolism. However, the relationship between chronic glucocorticoid exposure, the gut microbiota, and brain metabolism remains largely unknown. In this study, we first investigated the effects of chronic corticosterone exposure on various domains of behavior in adult male C57BL/6J mice treated with the glucocorticoid corticosterone to evaluate them as an animal model of depression. We then examined the gut microbial composition and brain and plasma metabolome in corticosterone-treated mice. Chronic corticosterone treatment resulted in reduced locomotor activity, increased anxiety-like and depression-related behaviors, decreased rotarod latency, reduced acoustic startle response, decreased social behavior, working memory deficits, impaired contextual fear memory, and enhanced cued fear memory. Chronic corticosterone treatment also altered the composition of gut microbiota, which has been reported to be associated with depression, such as increased abundance of Bifidobacterium, Turicibacter, and Corynebacterium and decreased abundance of Barnesiella. Metabolomic data revealed that long-term exposure to corticosterone led to a decrease in brain neurotransmitter metabolites, such as serotonin, 5-hydroxyindoleacetic acid, acetylcholine, and gamma-aminobutyric acid, as well as changes in betaine and methionine metabolism, as indicated by decreased levels of adenosine, dimethylglycine, choline, and methionine in the brain. These results indicate that mice treated with corticosterone have good face and construct validity as an animal model for studying anxiety and depression with altered gut microbial composition and brain metabolism, offering new insights into the neurobiological basis of depression arising from gut-brain axis dysfunction caused by prolonged exposure to excessive glucocorticoids.
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Neurology Neuroimmunology & Neuroinflammation, 11(3), May, 2024 Peer-reviewed
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eLife, 12, Mar 26, 2024 Peer-reviewedIncreased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimer’s disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.
Misc.
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伊川正人, 高橋 智, 若菜茂晴／編, 羊土社, Nov, 2016
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The Japanese Journal of Psychonomic Science, 32(1) 101-119, Sep, 2013Maturation and integration of neurons and grial cells in the hippocampus is considered to be essential for regulating endocrine, affective, and congnitive functions, and the disruption of such process may cause mental illness. Previously, we have reported that mice heterozygous for a null mutation in α-CaMKII, which has a key role in a synaptic plasticity, show abnormal behaviors related to psychiatric disorders, such as schizophrenia and bipolar disorder. In these mutant mice, almost all neurons in the dentate gyrus are at a pseudo-immature properties, whihc we referred to as "immature dentate gyrus (iDG)." To date, the iDG phenotype have been found in mustant strains including Schnurri-2 knockout, SNAP-25 mutant, and forebrain-specific calcineurin knockout mice which show similar behavioral phenotypes. In addition, both chronic fluoxetine treatment and pilocarpine-induced seizures can reverse the maturation state of the mature neurons, resulting in the iDG phenotype in wild-type mice. Such iDG-like phenomenon was observed in the brains from patients with schizophrenia/bipolar disorder. Based on the findings, we proposed that the iDG is a potential new endophenotype of neuropsychiatric disorders. This review summarizes the behavioral abnormalities, iDG phenotype, and the implications in the pathophysiology of neuropsychiatric disorders.
Presentations
1Teaching Experience
2Professional Memberships
3Research Projects
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科学研究費助成事業, 日本学術振興会, Apr, 2024 - Mar, 2027