Faculty Profiles - MATSUMOTO Yosuke

Papers - MATSUMOTO Yosuke

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Layer- and region-specific distribution of chondroitinase-resistant, lectin-binding extracellular matrix structures in the mouse somatosensory cortex and hippocampus. Reviewed International journal

Hiroshi Ueno, Eriko Kitano, Sachiko Mori, Yu Takahashi, Shinji Murakami, Kenta Wani, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara

Neuroscience 2025.8

Language：English Publishing type：Research paper (scientific journal)

Extracellular matrix (ECM) structures in the brain, including perineuronal nets (PNNs), contribute to synaptic plasticity, neuroprotection, and circuit stability. Wisteria floribunda agglutinin (WFA) is widely used to label PNNs but detects only a subset of ECM glycoconjugates. To better understand ECM composition and organization, we used a panel of plant-derived lectins with distinct glycan-binding specificities to examine the spatial distribution of ECM in the mouse primary somatosensory cortex and hippocampus. Brain sections from adult male C57BL/6N mice (n = 6) were stained using seven biotinylated lectins (Jacalin, PSA, AAL, LCA, WGA, PHA-E, and PHA-L). Confocal imaging and quantitative fluorescence analysis revealed that each lectin exhibited a unique pattern of ECM labeling. Several lectins, such as Jacalin, WGA, and PHA-E, showed strong labeling in superficial cortical layers and select hippocampal subfields, while others displayed more diffuse or subregion-specific distributions. Co-labeling with WFA demonstrated partial overlap with some lectins but also revealed non-overlapping ECM components. Notably, most lectin signals, including those forming perineuronal net-like structures, remained intact after chondroitinase ABC digestion, in contrast to the loss of WFA staining. These results highlight the molecular heterogeneity and anatomical specificity of brain ECM structures, revealing a chondroitin sulfate-independent scaffold not visualized by WFA. These results highlight the molecular heterogeneity and anatomical specificity of brain ECM structures. Using diverse lectins provides complementary information to WFA-based labeling and reveals broader ECM architectures. This approach offers new insights into region- and layer-specific ECM organization, with implications for understanding the differential plasticity, resilience, and vulnerability of brain circuits.

DOI： 10.1016/j.neuroscience.2025.08.017

Postnatal expression of Cat-315-positive perineuronal nets in the SAMP10 mouse primary somatosensory cortex. Reviewed International journal

Hiroshi Ueno, Yu Takahashi, Sachiko Mori, Eriko Kitano, Shinji Murakami, Kenta Wani, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara

IBRO neuroscience reports 18 244 - 256 2025.6

Language：English Publishing type：Research paper (scientific journal)

Perineuronal nets (PNNs) form at the end of the critical period of plasticity in the mouse primary somatosensory cortex. PNNs are said to have functions that control neuroplasticity and provide neuroprotection. However, it is not clear which molecules in PNNs have these functions. We have previously reported that Cat-315-positive molecules were not expressed in the PNNs of the senescence-accelerated model (SAM)P10 strain model mice at 12 months of age. To confirm whether the loss of Cat-315-positive molecules occurred early in life in SAMP10 mice, we examined Cat-315-positive PNNs in the primary somatosensory cortex during postnatal development. This research helps to elucidate the function of PNNs and the mechanism of cognitive decline associated with ageing. To confirm whether Cat-315-positive PNNs changed in an age-dependent manner in SAMP10 mice, we examined the primary somatosensory cortex at 21, 28, and 56 days after birth. We compared these results with those of senescence-accelerated mouse-resistant (SAMR) mice. In SAMP10 mice, Cat-315-positive PNNs were expressed in the primary somatosensory cortex early after birth, but their expression was significantly lower than that in SAMR1 mice. Many other molecules that calibrated the PNN were unchanged between SAMP10 and SAMR1 mice. This study revealed that the expression of the Cat-315 epitope was decreased in the primary somatosensory cortex of SAMP10 mice during postnatal development. SAMP10 mice have had histological abnormalities in their brains since early life. Furthermore, using SAMP10 will be useful in elucidating the mechanism of age-related abnormalities in brain function as well as in elucidating the function and structure of PNNs.

DOI： 10.1016/j.ibneur.2025.01.012

Postnatal sleep restriction in male mice impairs the development of parvalbumin-positive neurons in the prefrontal cortex and increases anxiety-like behaviour. Reviewed International journal

Eriko Kitano, Hiroshi Ueno, Yu Takahashi, Sachiko Mori, Shinji Murakami, Kenta Wani, Yosuke Matsumoto, Ayaka Ochi, Tsukasa Hatano, Motoi Okamoto, Takeshi Ishihara

Neuroscience 573 127 - 142 2025.5

Language：English Publishing type：Research paper (scientific journal)

Sleep is crucial for maintaining homeostasis and is conserved across the animal kingdom. Sleep restriction has emerged as a significant health concern, particularly in adolescents and adults. In infants and children, it is linked to disrupted brain development, impaired social-emotional growth, deficits in executive function, and increased anxiety and depression. However, the precise biological mechanisms remain unclear. This study aimed to investigate the effects of sleep restriction on parvalbumin (PV)-expressing inhibitory interneurons, which mature postnatally, and to clarify some of the developmental consequences of sleep restriction on brain function. Three hours of sleep restriction was induced daily from postnatal day (P) 10 until P14, P21, and P28. Behavioural abnormalities were assessed on P21, followed by brain histology and behavioural recovery analysis after sleep restoration. Our results showed that sleep restriction did not alter the development of PV-positive neurons in the somatosensory cortex or amygdala but significantly reduced PV-positive neurons in the prefrontal cortex. Moreover, sleep-restricted mice exhibited increased anxiety-like behaviour at P21. Upon sleep restoration, adult mice showed reduced activity in the open field test, indicating a persistent effect of early-life sleep restriction. These findings suggest that sleep restriction during postnatal development selectively affects certain brain regions, with potential long-lasting consequences. Early intervention to mitigate sleep restriction's impact on brain development may be crucial for reducing neurodevelopmental deficits.

DOI： 10.1016/j.neuroscience.2025.03.029

Rearing in an envy-like environment increases anxiety-like behaviour in mice. Reviewed International journal

Hiroshi Ueno, Eriko Kitano, Yu Takahashi, Sachiko Mori, Shinji Murakami, Kenta Wani, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara

Translational neuroscience 16 ( 1 ) 20220364 - 20220364 2025.1

Language：English Publishing type：Research paper (scientific journal)

Interest in the societal and psychological harm caused by widespread envy and social comparison is increasing. Envy is associated with anxiety and depression, though the mechanism by which envy affects neuropsychiatric disorders, such as depression, remains unclear. Clarifying the neurobiological basis of envy's effects on behaviour and emotion regulation in experimental mice is essential for developing disease-prevention and treatment strategies. As mice recognize other mice in neighbouring cages, this study investigated whether they recognize neighbouring cages housed in environmentally enriched cages and suffer psychological stress due to envy. After being raised in an envy-like environment for 3 weeks, we revealed changes in the behaviour of the mice through a series of behavioural experiments. Mice raised in an envious environment showed increased body weight and anxiety-like behaviour but decreased social behaviour and serum corticosterone levels compared to control mice. Thus, mice recognize their neighbouring cages and experience psychological stress due to envy. This study revealed a part of the scientific basis for why envy increased anxiety. Using this novel experimental breeding environment, it may be possible to create an experimental animal model of anxiety disorders.

DOI： 10.1515/tnsci-2022-0364

Age-related behavioural abnormalities in C57BL/6.KOR-Apoe shl mice. Reviewed International journal

Hiroshi Ueno, Yu Takahashi, Sachiko Mori, Eriko Kitano, Shinji Murakami, Kenta Wani, Tetsuji Miyazaki, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara

Translational neuroscience 16 ( 1 ) 20220363 - 20220363 2025.1

Language：English Publishing type：Research paper (scientific journal)

Spontaneously hyperlipidaemic (Apoeshl) mice were discovered in 1999 as mice lacking apolipoprotein E (ApoE) owing to a mutation in the Apoe gene. However, age-related behavioural changes in commercially available Apoeshl mice have not yet been clarified. The behavioural abnormalities of ApoE-deficient mice, which are genetically modified mice artificially deficient in ApoE, have been investigated in detail, and it has been reported that they can serve as a model of Alzheimer's disease (AD). To understand whether Apoeshl mice can also serve as a murine model of AD, it is necessary to investigate age-related behavioural abnormalities in Apoeshl mice. In this study, we conducted a series of behavioural experiments on 7- and 11-month-old Apoeshl mice to investigate the behavioural abnormalities associated with ageing in Apoeshl mice. In this study, 7-month-old Apoeshl mice showed decreased body weight and grip strength compared to age-matched wild-type mice. In the open field test, 7-month-old Apoeshl mice showed increased anxiety-like behaviour compared to wild-type mice, whereas 11-month-old Apoeshl mice showed decreased anxiety-like behaviour. Moreover, Apoeshl mice aged 7 and 11 months had increased serum cholesterol levels. These results indicate that the behaviour of Apoeshl mice changes with age. However, 11-month-old Apoeshl mice did not show a decline in cognitive function or memory ability similar to murine models of AD. Our findings indicate that Apoeshl mice can be used to investigate the function of ApoE in the central nervous system.

DOI： 10.1515/tnsci-2022-0363

【LGBTQ+の子どもたち～多様な性を知ろう～】性別違和感をもつ子どもと二次性徴抑制療法

長谷川高誠, 松本洋輔, 中塚幹也

チャイルドヘルス 27 ( 9 ) 679 - 682 2024.9

Forgetfulness in adult attention‐deficit/hyperactivity disorder masks transient epileptic amnesia: a case report Reviewed International journal

Takashi Fukao, Masaki Fujiwara, Yuto Yamada, Shinji Sakamoto, Yosuke Matsumoto, Manabu Takaki

Psychiatry and Clinical Neurosciences Reports 3 ( 3 ) e70003 2024.8

Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley

Abstract

Background

Inattention due to attention‐deficit/hyperactivity disorder (ADHD) can lead to forgetfulness. Transient epileptic amnesia (TEA) can cause forgetfulness, similar to ADHD. We report a patient with ADHD who developed TEA.

Case Presentation

The patient was a 40‐year‐old woman with ADHD. She has been prone to forgetfulness since childhood. Two years before visiting our outpatient clinic, she had begun to occasionally forget events that had occurred several days earlier. However, she was largely unaware of the emergence of new amnestic symptoms. She had also begun to experience various other amnestic symptoms 2 months before she visited our clinic, which prompted her to visit our outpatient clinic. The combination of a detailed interview, electroencephalography (EEG) examination, and consideration of TEA enabled us to diagnose her with TEA and provide treatment accordingly. In our patient, daily forgetfulness due to ADHD delayed the recognition of new additional forgetfulness attributed to TEA.

Conclusion

Psychiatrists need to consider TEA when patients with ADHD present with changes in or exacerbation of forgetfulness.

DOI： 10.1002/pcn5.70003

Trans men can achieve adequate muscular development through low-dose testosterone therapy: A long-term study on body composition changes. Reviewed International journal

Yusuke Tominaga, Tomoko Kobayashi, Yuko Matsumoto, Takatoshi Moriwake, Yoshitaka Oshima, Misa Okumura, Satoshi Horii, Takuya Sadahira, Satoshi Katayama, Takehiro Iwata, Shingo Nishimura, Kensuke Bekku, Kohei Edamura, Morito Sugimoto, Yasuyuki Kobayashi, Masami Watanabe, Yuzaburo Namba, Yosuke Matsumoto, Mikiya Nakatsuka, Motoo Araki

Andrology 13 ( 2 ) 275 - 285 2024.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Transgender individuals undergo the gender-affirming hormone therapy (GAHT) to achieve physical changes consistent with their gender identity. Few studies are available on the long-term safety and efficacy of GAHT. OBJECTIVES: To investigate the long-term physical effects and the safety of the testosterone therapy for trans men and to assess the impact of differential hormone dose. MATERIALS AND METHODS: Trans men who initiated GAHT between May 2000 and December 2021 were included in this retrospective analysis. Physical findings (body mass index, body fat percentage (BFP), lean body mass (LBM), and grip strength), blood testing results (hemoglobin, hematocrit, uric acid, creatinine, total cholesterol, triglycerides, and total testosterone), and menstrual cessation were recorded. We assessed the effects of testosterone on body composition changes and laboratory parameters, comparing a low-dose group (≤ 62.5 mg/wk) to a high-dose group (> 62.5 mg/wk). RESULTS: Of 291 participants, 188 patients (64.6%) were in the low-dose group and 103 (35.4%) in the high-dose group. Cumulative menstrual cessation rates up to 12 months were not significantly different between groups. Both groups showed a decrease in BFP and an increase in LBM during the first year of therapy, followed by a slight increase in both over the long term. The high-dose group exhibited greater LBM gains during the first year. Higher hormone doses and lower initial LBM values were associated with LBM increases at 3 and 6 months (3 mo, P = 0.006, P < 0.001; 6 mo, P = 0.015, P < 0.001). There were no long-term, dose-dependent side effects such as polycythemia or dyslipidemia. CONCLUSION: Long-term GAHT for trans men is safe and effective. Low-dose testosterone administration is sufficient to increase LBM in trans men. Higher testosterone doses can lead to an earlier increase in muscle mass.

DOI： 10.1111/andr.13640

Mice Recognise Mice in Neighbouring Rearing Cages and Change Their Social Behaviour. Reviewed International journal

Hiroshi Ueno, Yu Takahashi, Sachiko Mori, Shinji Murakami, Kenta Wani, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara

Behavioural neurology 2024 9215607 - 9215607 2024

Language：English Publishing type：Research paper (scientific journal)

Mice are social animals that change their behaviour primarily in response to visual, olfactory, and auditory information from conspecifics. Rearing conditions such as cage size and colour are important factors influencing mouse behaviour. In recent years, transparent plastic cages have become standard breeding cages. The advantage of using a transparent cage is that the experimenter can observe the mouse from outside the cage without touching the cage. However, mice may recognise the environment outside the cage and change their behaviour. We speculated that mice housed in transparent cages might recognise mice in neighbouring cages. We used only male mice in this experiment. C57BL/6 mice were kept in transparent rearing cages with open lids, and the cage positions were maintained for 3 weeks. Subsequently, we examined how mice behaved toward cagemate mice, mice from neighbouring cages, and mice from distant cages. We compared the level of interest in mice using a social preference test. Similar to previous reports, subject mice showed a high degree of interest in unfamiliar mice from distant cages. By contrast, subject mice reacted to mice from neighbouring cages as familiar mice, similar to cagemate mice. This suggests that mice housed in transparent cages with open lids perceive the external environment and identify mice in neighbouring cages. Researchers should pay attention to the environment outside the mouse cage, especially for the social preference test.

DOI： 10.1155/2024/9215607

Effects of home-cage elevation on behavioral tests in mice. Reviewed International journal

Hiroshi Ueno, Yu Takahashi, Shinji Murakami, Kenta Wani, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara

Brain and behavior 14 ( 2 ) e3269 2023.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Research reproducibility is a common problem in preclinical behavioral science. Mice are an important animal model for studying human behavioral disorders. Experimenters, processing methods, and rearing environments are the main causes of data variability in behavioral neuroscience. It is likely that mice adapt their behavior according to the environment outside the breeding cage. We speculated that mice housed on elevated shelves and mice housed on low shelves might have differently altered anxiety-like behavior toward heights. PURPOSE: The purpose of this study was to investigate potential behavioral changes in mice raised at different heights for 3 weeks. Changes in behavior were examined using various experimental tests. RESULTS: Mice housed on elevated shelves showed reduced anxiety-like behavior in a light/dark traffic test compared with mice housed on low shelves. There were no significant differences between the two groups in terms of activity, exploratory behavior, muscle strength, or depression-like behavior. CONCLUSIONS: Our results indicate that different cage heights and corresponding light exposure may alter the anxiety-like behavior of mice in response to brightness. Researchers need to carefully control the cage height and light intensity experienced by the mice to produce reproducible test results.

DOI： 10.1002/brb3.3269

岡山大学病院ジェンダーセンターにおける二次性徴抑制療法の臨床的検討 Reviewed

小林知子, 松本裕子, 中塚幹也, 新井富士美, 長谷川高誠, 松本洋輔, 大島義孝, 佐藤俊樹, 難波祐三郎

GID(性同一性障害)学会雑誌 16 ( 1 ) 25 - 30 2023.12

生体移植ドナーの精神的・身体的サポート生体肝移植ドナーの併存精神疾患と精神科連携

木村宏之, 杉田尚子, 大橋綾子, 成田尚, 藤澤大介, 岡田剛史, 松本洋輔, 岸辰一, 川崎弘詔, 西村勝治, 小倉靖弘, 池田匡志, 日本総合病院精神医学会臓器不全・移植関連委員会

移植 58 ( 総会臨時 ) 116 - 116 2023.9

Component-specific reduction in perineuronal nets in senescence-accelerated mouse strains. Reviewed International journal

Hiroshi Ueno, Yu Takahashi, Shinji Murakami, Kenta Wani, Tetsuji Miyazaki, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara

IBRO neuroscience reports 14 111 - 121 2023.6

Language：English Publishing type：Research paper (scientific journal)

With increased life expectancy, age-related diseases are a significant health concern in Western societies. Animal models (e.g., rodents) have been used to understand age-related changes in brain function-particularly through the senescence-accelerated mouse (SAM) strain. Previous reports have shown that the senescence-accelerated mouse propensity (SAMP)8 and SAMP10 strains have learning disabilities. In this study, we analyzed the prefrontal cortex, which is involved in cognitive function. We aimed to clarify the changes in parvalbumin-positive interneurons (PV-positive neurons), which are related to cognitive function, and perineuronal nets (PNNs), which are special extracellular matrix molecules formed around them. We performed histological analysis of PV-positive neurons and PNNs in the prefrontal cortex to elucidate the mechanism of behavioral abnormalities in SAMP8 and SAMP10 strains. Expression of Cat-315-positive PNN was not confirmed in the prefrontal cortex of SAMP10 mice. However, the density of AB1031-positive PNN, tenascin-R-positive PNN, and brevican-positive PNN decreased in the prefrontal cortex of SAMP8 and SAMP10 mice compared to that of the senescence-accelerated mouse resistance (SAMR1) mice. In addition, the density of PV-positive neurons was lower in SAMP8 mice than in SAMR1 mice. These mice, which exhibited behavioral and neuropathological phenotypes with age, showed different PV-positive neurons and PNNs in the prefrontal cortex compared with the SAMR1 mice. We believe that the results of this study will be useful for elucidating the mechanisms of age-related decline in cognitive and learning functions using SAM.

DOI： 10.1016/j.ibneur.2023.01.002

Comprehensive behavioral study of C57BL/6.KOR-ApoE^shl mice Reviewed International journal

Hiroshi Ueno, Yu Takahashi, Shinji Murakami, Kenta Wani, Tetsuji Miyazaki, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara

Translational Neuroscience 14 ( 1 ) 20220284 - 20220284 2023.1

Language：English Publishing type：Research paper (scientific journal) Publisher：Walter de Gruyter GmbH

Abstract

Background

Apolipoprotein E (ApoE) is associated with Alzheimer’s disease (AD) and cognitive dysfunction in elderly individuals. There have been extensive studies on behavioral abnormalities in ApoE-deficient (Apoe^shl) mice, which have been described as AD mouse models. Spontaneously hyperlipidemic mice were discovered in 1999 as ApoE-deficient mice due to ApoE gene mutations. However, behavioral abnormalities in commercially available Apoe^shl mice remain unclear. Accordingly, we aimed to investigate the behavioral abnormalities of Apoe^shl mice.

Results

Apoe^shl mice showed decreased motor skill learning and increased anxiety-like behavior toward heights. Apoe^shl mice did not show abnormal behavior in the Y-maze test, open-field test, light/dark transition test, and passive avoidance test.

Conclusion

Our findings suggest the utility of Apoe^shl mice in investigating the function of ApoE in the central nervous system.

DOI： 10.1515/tnsci-2022-0284

Other Link： https://www.degruyter.com/document/doi/10.1515/tnsci-2022-0284/pdf

Fingolimod increases parvalbumin-positive neurons in adult mice Reviewed International journal

Hiroshi Ueno, Yu Takahashi, Shinji Murakami, Kenta Wani, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara

IBRO Neuroscience Reports 13 96 - 106 2022.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

In recent years, it has been shown that central nervous system agents, such as antidepressants and antiepileptic drugs, reopen a critical period in mature animals. Fingolimod, which is used for the treatment of multiple sclerosis, also restores neuroplasticity. In this study, we investigated the effects of parvalbumin (PV)-positive neurons and perineuronal nets (PNN) on fingolimod administration with respect to neuroplasticity. Fingolimod was chronically administered intraperitoneally to mature mice. PV-positive neurons and PNN in the hippocampus, prefrontal cortex, and somatosensory cortex were analyzed. An increase in PV-positive neurons was observed in the hippocampus, prefrontal cortex, and somatosensory cortex of the fingolimod-treated mice. An increase in Wisteria floribunda agglutinin-positive PNN was confirmed in mice treated with fingolimod in the somatosensory cortex only. Fingolimod increased the density of PV-positive neurons in the brains of mature mice. The results indicate that fingolimod may change the critical period in mature animals.

DOI： 10.1016/j.ibneur.2022.06.005

The Prevention of Home-Cage Grid Climbing Affects Muscle Strength in Mice Reviewed International journal

Ueno H, Takahashi Y, Murakami S, Wani K, T Miyazaki, Matsumoto Y, Okamoto M, Ishihara T

Scientific Reports 12 ( 15263 ) 15263 - 15263 2022.9

Language：English Publishing type：Research paper (scientific journal)

Experimenters and treatment methods are the major contributors to data variability in behavioral neuroscience. However, home cage characteristics are likely associated with data variability. Mice housed in breeding cages spontaneously exhibit behavioral patterns such as biting into the wire grid and climbing on the grid lid. We aimed to clarify the effect of covering the stainless steel wire grid lid in commonly used home cage with Plexiglas to prevent climbing on muscle strength in mice. Furthermore, we investigated the effects of climbing prevention on activity and anxiety-like behavior, and the impact of climbing prevention during the postnatal development period and adulthood on muscle strength. Muscle strength, anxiety-like behavior, and locomotor activity were assessed by a battery of tests (wire hang, suspension, grip strength, rotarod, elevated-plus maze, and open field tests). Mice prevented from climbing the wire grid during postnatal development displayed lower muscle strength than those able to climb. Moreover, mice prevented from climbing for 3 weeks following maturity had weakened muscles. The muscle strength was decreased with 3 weeks of climbing prevention in even 1-year-old mice. In summary, the stainless steel wire grid in the home cage contributed to the development and maintenance of muscle strength in mice.

DOI： 10.1038/s41598-022-19713-4

Prevalence of Gender Dysphoria by Gender and Age in Japan: A Population-Based Internet Survey Using the Utrecht Gender Dysphoria Scale Reviewed International journal

Yoshitaka Oshima, Yosuke Matsumoto, Seishi Terada, Norihito Yamada

The Journal of Sexual Medicine 19 ( 7 ) 1185 - 1195 2022.7

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

BACKGROUND: Several studies have attempted to estimate the prevalence of gender dysphoria (GD) from a general population sample. However, no previous studies used reliable questionnaires. AIM: To estimate the prevalence of GD in Japan by gender and age using the Utrecht Gender Dysphoria Scale (UGDS). METHODS: A cross-sectional observational study was conducted with 20,000 respondents between the ages of 20 and 69 who were registered with an internet research company. The study consisted of two phases. First, the participants were asked to self-identify their gender on two 5-point Likert scales. Second, the screened participants completed the UGDS. OUTCOMES: Self-identified gender and GD were defined as follows: ambivalent gender (equally feeling like the birth gender and another gender), incongruent gender (a stronger sense of the latter vs the former), narrow GD (incongruent gender + UGDS score ≥ 41), and broad GD (ambivalent or incongruent gender + UGDS score ≥ 41). RESULTS: Among the eligible participants, the age-adjusted proportions of those classified as male (n = 7827) and female (n = 8903) at birth were 6.0% and 5.9%, respectively, for ambivalent gender, and 0.93% and 1.0%, respectively, for incongruent gender. The age-adjusted prevalence of GD was 0.27% (95% confidence interval, 0.18-0.42) and 0.35% (95% confidence interval, 0.25-0.50) for narrow GD and 0.87% (95% confidence interval, 0.69-1.1) and 1.1% (95% confidence interval, 0.86-1.3) for broad GD, respectively. No significant gender differences were found within the age groups, except for broad GD in respondents in their 50s (P = .016). However, for both genders, significant differences were found between age groups such that GD was more prevalent in younger vs older respondents, except for broad GD in respondents classified as female at birth (P = .063). CLINICAL IMPLICATIONS: Clinicians should be aware that the prevalence of GD is not negligible and that it varies with age. GD should be assessed in detail from various perspectives in addition to self-identified gender. STRENGTHS & LIMITATIONS: This study used a reliable questionnaire to examine the prevalence of GD in a large population. However, the participants did not represent the general population because this was an internet survey. CONCLUSION: The prevalence of GD was much higher than previously estimated by clinic-based studies, and was more frequently associated with participant age vs gender. Oshima Y, Matsumoto Y, Terada S, et al. Prevalence of Gender Dysphoria by Gender and Age in Japan: A Population-based Internet Survey Using the Utrecht Gender Dysphoria Scale. J Sex Med 2022;19:1185-1195.

DOI： 10.1016/j.jsxm.2022.03.605

Effect of simultaneous testing of two mice in the tail suspension test and forced swim test Reviewed International journal

Hiroshi Ueno, Yu Takahashi, Shinji Murakami, Kenta Wani, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara

Scientific Reports 12 ( 1 ) 9224 - 9224 2022.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Abstract

In mouse studies, the results of behavioural experiments are greatly affected by differences in the experimental environment and handling methods. The Porsolt forced swim test and tail suspension test are widely used to evaluate predictive models of depression-like behaviour in mice. It has not been clarified how the results of these tests are affected by testing single or multiple mice simultaneously. Therefore, this study evaluated the differences between testing two mice simultaneously or separately. To investigate the effect of testing multiple mice simultaneously, the Porsolt forced swim test and tail suspension test were performed in three patterns: (1) testing with an opaque partition between two mice, (2) testing without a partition between two mice, and (3) testing a single mouse. In the Porsolt forced swim test, the mice tested simultaneously without a partition demonstrated increased immobility time as compared to mice tested alone. No difference in immobility time was observed between the three groups in the tail suspension test. Our results showed that the environment of behavioural experiments investigating depression-like behaviour in mice can cause a difference in depression-like behaviour. The results of this experiment indicated that it is necessary to describe the method used for behavioural testing in detail.

DOI： 10.1038/s41598-022-12986-9

Other Link： https://www.nature.com/articles/s41598-022-12986-9

Mice can recognise water depths and will avoid entering deep water. International journal

Hiroshi Ueno, Yu Takahashi, Shunsuke Suemitsu, Shinji Murakami, Naoya Kitamura, Kenta Wani, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara

Translational neuroscience 13 ( 1 ) 1 - 10 2022.1

Language：English Publishing type：Research paper (scientific journal)

Rodents are averse to bodies of water, and this aversion has been exploited in experiments designed to study stress in mice. However, a few studies have elucidated the characteristics of murine water aversion. In this study, we investigated how mice behave in and around areas filled with water. Using variants of the open field test that contained pools of water at corners or sides of the field, we recorded the movements of mice throughout the field under various conditions. When the water was 8 mm deep, the mice explored the water pool regardless of whether an object was placed within it, but when the water was 20 mm deep, the mice were less willing to enter it. When the mice were placed on a dry area surrounded by 3 mm-deep water, they explored the water, but when they were surrounded by 8 mm-deep water, they stayed within the dry area. Our results indicate that mice exhibit exploratory behaviours around water, they can recognise water depths and avoid unacceptably deep water, and their willingness to enter water may be reduced by situational anxiety. Our experimental method could be used to investigate water-related anxiety-like behaviours in mice.

DOI： 10.1515/tnsci-2020-0208

Chronic Inhibition of Aggressive Behavior Induces Behavioral Change in Mice. International journal

Hiroshi Ueno, Yu Takahashi, Shinji Murakami, Kenta Wani, Tetsuji Miyazaki, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara

Behavioural neurology 2022 7630779 - 7630779 2022

Language：English Publishing type：Research paper (scientific journal)

Suppression of anger is more common than its expression among Asian individuals. Emotional suppression is considered an unhealthy emotional regulation. Most studies on emotional suppression have concluded that suppression adversely affects social outcomes, with approximately 5% of the world's population suffering from emotional disorders. However, anger suppression has not received academic attention, and details of the effects of chronic anger suppression on the central nervous system remain unclear. In this study, we performed the resident-intruder test to investigate the effect of chronic suppression of aggressive behavior in mice using a behavioral test battery and to clarify whether suppression of this aggressive behavior is stressful for mice. Mice chronically inhibited aggressive behavior and lost weight. Mice with inhibited aggressive behavior showed a reduced percentage of immobility time during the tail suspension test as well as no changes in activity, anxiety-like behavior, muscle strength, or temperature sensitivity. This study provides scientific evidence for the effects of chronic aggressive behavior inhibition on the body and central nervous system.

DOI： 10.1155/2022/7630779

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