Biology subjects

Matsuyama, S.

Publications and source records attributed to Matsuyama, S..

13 recordsLinked to original sources

bioRxiv2026

Acute inflammation-mediated attenuation of behavioural sensitization in methamphetamine-sensitized mice via distinct COX-2 and TNF-α pathways

Background and PurposeWhile inflammation has been generally considered to exacerbate symptoms of schizophrenia, some clinical observations suggest that acute inflammation may alleviate positive symptoms. However, animal models often use excessive inflammatory stimuli, and the effects of acute inflammation--comparable to levels observed in patients--remain unknown. Experimental ApproachTo address this, we examined whether acute inflammation induced under relatively mild, clinically relevant conditions suppresses behavioural sensitization in methamphetamine (METH)-sensitized mice, a model of psychostimulant-induced psychosis with relevance to certain aspects of positive symptoms of schizophrenia. We used a repeated METH (1 mg/kg) sensitized model to evaluate the effects of acute inflammation on behavioural sensitization. Acute inflammation was induced via two methods using either lipopolysaccharides (LPS; 1 g/kg) to mimic peripheral immune activation or restraint stress (RS; single 2-h exposure) to model the neuroinflammation induced by psychological stress. LPS doses were adjusted with reference to the magnitude of peripheral cytokine elevation reported in patients, and RS was applied in short single sessions to avoid excessive inflammation. Key ResultsBoth LPS and RS significantly suppressed behavioural sensitization, without inducing other behavioural abnormalities. This suppression was dependent on toll-like receptor-4 activation. LPS-mediated suppression involved cyclooxygenase-2, whereas RS-mediated suppression was linked to the microglia-derived tumour necrosis factor-. LPS did not alter, whereas RS significantly reduced the striatal extracellular dopamine levels. Conclusion and ImplicationsThese findings suggest that acute inflammation suppresses behavioural sensitization through distinct mechanisms depending on the inflammatory trigger, providing a framework for understanding how inflammation may influence psychosis-related processes, with potential relevance to schizophrenia.

pharmacology and toxicology↗

bioRxiv2026

Macrophages regulate meiotic initiation and germ cell clearance in the developing ovary

Tissue-resident macrophages are increasingly recognized for their roles in promoting organogenesis, yet how macrophages are involved in fetal ovarian development remains unclear. In particular, little is known about ovarian macrophage ontogeny and how it relates to germ cell entry into meiosis and establishment of the oocyte reserve. Here we combine temporally-controlled lineage tracing of yolk-sac erythro-myeloid progenitors, fetal HSC-derived progenitors, and postnatal monocytes to map multi-wave seeding and remodeling of ovarian macrophages across fetal and early postnatal life. We identify three major resident subsets defined by MHCII and CSF1R that display distinct expansion kinetics and persistence, and we show that CCR2-dependent monocyte recruitment is required for efficient maturation of postnatal macrophage populations. Functionally, transient or sustained depletion of CSF1R fetal macrophages perturbs ovarian vascular growth and triggers precocious meiotic initiation without overt loss of germ cells, leading to persistent, premature meiotic progression. Extending macrophage depletion into late gestation disrupts perinatal physiological germ cell attrition despite rapid postnatal macrophage repopulation. Together, our findings establish ovarian macrophages as stage-specific regulators that couple immune ontogeny to ovarian morphogenesis and germ cell quality control during establishment of the oocyte reserve. One Sentence SummaryOvarian macrophages are required for the proper timing of germ cell meiotic entry and progression, vascular growth, and for the physiological clearance of germ cells during establishment of the oocyte reserve in perinatal stages.

developmental biology↗

bioRxiv2026

Prenatal corticosteroid exposure disrupts vascular-immune interactions and impairs steroidogenesis in the fetal testis

Antenatal corticosteroid (ACS) therapy, typically using dexamethasone (Dex), is a cornerstone of improving preterm infant survival by accelerating lung maturation. However, its systemic effects on other developing organs remain poorly understood. Here, we reveal a previously unrecognized impact of prenatal Dex exposure on fetal testis development, with implications for long-term male reproductive health. Analysis of fetal testes from a Dex-based ACS mouse model revealed that Dex suppressed androgen synthesis by reducing Leydig cell number and downregulating steroidogenic pathways. Dex also activated immune programs, inducing CD163 M2 macrophages and IL10 signaling, which promoted endothelial expansion. Despite these pro-angiogenic signals, vascular architecture was disrupted: capillary density and pericyte coverage declined, while blood vessel diameter increased. Transcriptomic analyses revealed downregulation of androgen response and cholesterol metabolism pathways, alongside upregulation of immune and coagulation signatures. Analyses of fetal ovaries revealed a sexually dimorphic and organ-specific effect of ACS therapy, in which ovarian gene expression remained unaffected. Our findings uncover an immune-vascular mechanism linking prenatal Dex exposure to impaired steroidogenesis, providing new insight into potentially broad effects of ACS therapy. One Sentence SummaryPrenatal corticosteroid exposure disturbs immune-vascular interactions and suppresses androgen synthesis in the fetal testis, revealing potentially widespread effects of a commonly used therapy.

developmental biology↗

bioRxiv2025

Comparative Analysis of Rumen Microbial Communities in Japanese Black Cattle: Site and Fertility Influences on Microbiome Composition and Function

IntroductionThe rumen microbiome plays a crucial role in nutrition, and productivity of cattle, influencing processes such as digestion, metabolism, and overall health. Understanding the composition and diversity of microbial communities within the rumen is essential for improving cattle management and enhancing the overall health outcomes. This study aims to investigate the rumen microbiome composition across two farms and fertility levels in Japanese Black beef cattle, using 16S rRNA amplicon sequencing. Differences in functional pathways between low- and normal-fertility cattle were also investigated. ResultCore ruminal microbes were identified with Bacteroidota being predominant across sites and fertility levels. Alpha and beta diversity metrics showed that the site explained a substantial variation in microbiome composition, while fertility had a minimal impact. Differential abundance analysis using LEfSe identified distinct microbial profiles for each site. Notably, taxa such as Fibrobacterota and Negativicutes were more abundant on one site, whereas Acholeplasmataceae and Lentisphaeria were more prevalent on the other site ConclusionUsing the sparse Partial Least Squares Discriminant Analysis (sPLS-DA) key taxa associated with fertility status, including Bradymonadales and Elusimicrobiaceae for low fertility and Anaerovoracaceae and Desulfovibrionaceae for normal fertility were identified. In addition, enhanced pathways in the normal fertility group include nicotinate degradation and complex sugar catabolism, while the low-fertility group showed increased activity in glycine betaine and nitrate reduction pathways, suggesting metabolic shifts and may impact reproductive efficiency. These findings underscore the complex interplay between geographic and biological factors in shaping the rumen microbiome.

microbiology↗

bioRxiv2024

Comprehensive expression data for two honey bee species, Apis mellifera and Apis cerana japonica

Comprehensive expression datasets were constructed for Apis mellifera and Apis cerana japonica. Post-oviposition day 6 to day 58 samples of A. mellifera workers (larva to adult); day 9, 10, 12, and 13 samples of A. mellifera queen (larva to pupa); and day 9 to day 18 samples of A. cerana japonica workers (larva to adult) were prepared, and RNA-Seq data were obtained. For A. cerana japonica, reference transcript sequence data, predicted amino acid sequence data, and functional annotation data were generated based on the genome sequence and RNA-Seq data. Using the transcript sequence and RNA-Seq data, comprehensive expression data for all transcripts of A. mellifera and A. cerana japonica were prepared. Hierarchical clustering analyses and the used sample preparation method ensured that both sets of expression data were reliable for use as comprehensive reference expression datasets. Therefore, these data are applicable for honey bee research or for comparative or evolutionary studies on insect species or social insect species at the genetic and molecular levels.

genetics↗

bioRxiv2023

Testis morphogenesis and fetal Leydig cell development are mediated through ERK signaling activated by platelet derived growth factor receptor alpha

Platelet derived growth factor receptor alpha (Pdgfra) plays a crucial role in the morphogenesis and differentiation of the fetal testis, but the molecular signaling involved in these processes remains unclear. Here, we use XY Pdgfra-null knock-in (KI) gonads to investigate the molecular mechanisms underlying Pdgfra-mediated testis cord formation and development of fetal Leydig cells (FLCs). The extracellular signal-regulated kinase (ERK) pathway, a well-known mitogen-activated protein kinase signaling pathway, was significantly inhibited in XY Pdgfra KI gonads, suggesting that ERK signaling is activated downstream of PDGFRA. Using ex vivo whole-organ culture, small interfering RNA (siRNA) cell culture methods, transwell assays and a genetic mouse model to disrupt ERK signaling in gonadal cells, we found that the ERK pathway promoted testis cord formation via early growth response 1 (Egr1)-mediated cell migration and regulated the expression of steroidogenic enzymes in FLCs via activating the transcription factor cAMP responsive element binding protein 1 (CREB; official name CREB1). These findings highlight the significance of PDGFRA and its downstream signaling in fetal testis morphogenesis and cellular differentiation, thus providing insights into the etiology of and potential therapeutic targets for disorders related to gonadal development.

developmental biology↗

bioRxiv2022

Development of novel cytoprotective small compounds inhibiting mitochondria-dependent apoptosis

We identified cyto-protective small molecules (CSMs) by a cell-based high-throughput screening of Bax inhibitors. Through a medicinal chemistry program, M109S was developed, which is orally bioactive and penetrates the blood-brain/retina barriers. M109S protected retinal cells in the mouse models of Stargardt disease and macular degeneration. M109S directly interacted with Bax and inhibited the conformational change and mitochondrial translocation of Bax. M109S inhibited ABT-737-induced apoptosis both in Bax-only and Bak-only MEFs. M109S also inhibited apoptosis induced by staurosporine (mouse embryonic fibroblasts), etoposide (Neuro2a cells), and obatoclax (ARPE19 cells). M109S is a novel small molecule protecting cells from mitochondria-dependent apoptosis both in vitro and in vivo. M109S has the potential to become a new research tool for studying cell death mechanisms and to develop therapeutics targeting mitochondria-dependent cell death pathway. (128words)

cell biology↗

bioRxiv2022

Use of the particle agglutination/particle agglutination-inhibition test for antigenic analysis of SARS-CoV-2

The antigenicity of SARS-CoV-2 is a critical issue for the effectiveness of the vaccine, and thus it should be phenotypically evaluated by serological assays as new field isolates emerge. The hemagglutination/hemagglutination-inhibition (HA/HI) tests are well-known as a representative method for antigenic analysis of influenza viruses, but SARS-CoV-2 is unlikely to agglutinate to human or guinea pig red blood cells. Therefore, the antigenic analysis requires complicated enzyme-linked immunosorbent assay (ELISA) or cell-based assays such as the microneutralization assay. In this study, we developed the particle agglutination/particle agglutination-inhibition (PA/PAI) test to easily and rapidly quantify the virus and antibody using human angiotensin-converting enzyme 2 (hACE2)-bound latex beads. The PA titer was positively correlated with the plaque-forming units. The PAI titer using post-infection Syrian hamster antisera clearly revealed the antigenic difference between the omicron and previous variants. The results show the PAI test is useful for easy and rapid antigenic analysis of SARS-CoV-2.

microbiology↗

bioRxiv2022

Female reproductive dormancy in Drosophila melanogaster is regulated by DH31-producing neurons projecting into the corpus allatum

Female reproductive dormancy in insects is a process that drastically suppresses oogenesis to conserve energy under adverse environments. In many insects, including the fruit fly, Drosophila melanogaster, reproductive dormancy is induced under low-temperature and short-day conditions by the downregulation of juvenile hormone (JH) biosynthesis by the corpus allatum (CA). Previous studies have suggested that brain neurons that project directly to the CA are important for the regulation of reproductive dormancy. However, the role of CA-projecting neurons in JH-mediated reproductive dormancy has not yet been confirmed by molecular genetic studies. In this study, we report that, in adult D. melanogaster, the neuropeptide diuretic hormone 31 (DH31) is produced by brain neurons that project into the CA. DH31-producing-CA-projecting neurons are connected downstream with a subset of circadian clock neurons, such as s-LNvs, which are known to be involved in reproductive dormancy regulation. The CA expresses the gene encoding the DH31 receptor, which is required for DH31-triggered elevation of intracellular cAMP in the CA. Knocking down Dh31 in these CA-projecting neurons or DH31 receptor in the CA leads to a failure in the decrease of the JH titer, normally observed under dormancy-inducing conditions, leading to abnormal yolk accumulation in the ovaries. Our findings provide the first molecular genetic evidence demonstrating that CA-projecting peptidergic neurons play an essential role in regulating reproductive dormancy by suppressing JH biosynthesis. Significance StatementDormancy is an adaptive physiological response to environmental changes that are unsuitable for survival. Adult females of many insect species undergo reproductive dormancy in which oogenesis is drastically arrested; it is induced by a decrease in juvenile hormone (JH) titers. However, we are yet to fully understand the molecular mechanisms underlying the control of JH biosynthesis under dormancy-inducing conditions. In this study using the fruit fly, we demonstrated that brain neurons projecting directly to the JH-producing organ, corpus allatum, play an essential role in regulating reproductive dormancy via the neuropeptide DH31. As the morphologically-similar neurons have previously been suggested to be involved in reproductive dormancy regulation, this study provides a fundamental molecular and neuronal basis for reproductive dormancy in insects.

physiology↗

bioRxiv2021

Viola: a structural variant signature extractor with user-defined classifications

Here, we present Viola, a Python package that provides structural variant (SV; large scale genome DNA variations that can result in disease, e.g., cancer) signature analytical functions and utilities for custom SV classification, merging multi-SV-caller output files, and SV annotation. We demonstrate that Viola can extract biologically meaningful SV signatures from publicly available SV data for cancer and we evaluate the computational time necessary for annotation of the data. AvailabilityViola is available on pip (https://pypi.org/project/Viola-SV/) and on GitHub (https://github.com/dermasugita/Viola-SV). Contactkdais-prm@m.u-tokyo.ac.jp

bioinformatics↗

bioRxiv2020

The inhaled steroid ciclesonide blocks SARS-CoV-2 RNA replication by targeting viral replication-transcription complex in culture cells

We screened steroid compounds to obtain a drug expected to block host inflammatory responses and MERS-CoV replication. Ciclesonide, an inhaled corticosteroid, suppressed replication of MERS-CoV and other coronaviruses, including SARS-CoV-2, the cause of COVID-19, in cultured cells. The effective concentration (EC90) of ciclesonide for SARS-CoV-2 in differentiated human bronchial tracheal epithelial cells was 0.55 M. Ciclesonide inhibited formation of double membrane vesicles, which anchor the viral replication-transcription complex in cells. Eight consecutive passages of 43 SARS-CoV-2 isolates in the presence of ciclesonide generated 15 resistant mutants harboring single amino acid substitutions in non-structural protein 3 (nsp3) or nsp4. Of note, ciclesonide still suppressed replication of all these mutants by 90% or more, suggesting that these mutants cannot completely overcome ciclesonide blockade. These observations indicate that the suppressive effect of ciclesonide on viral replication is specific to coronaviruses, highlighting it as a candidate drug for the treatment of COVID-19 patients. ImportanceThe outbreak of SARS-CoV-2, the cause of COVID-19, is ongoing. To identify the effective antiviral agents to combat the disease is urgently needed. In the present study, we found that an inhaled corticosteroid, ciclesonide suppresses replication of coronaviruses, including beta-coronaviruses (MHV-2, MERS-CoV, SARS-CoV, and SARS-CoV-2) and an alpha-coronavirus (HCoV-229E) in cultured cells. The inhaled ciclesonide is safe; indeed, it can be administered to infants at high concentrations. Thus, ciclesonide is expected to be a broad-spectrum antiviral drug that is effective against many members of the coronavirus family. It could be prescribed for the treatment of MERS, and COVID-19.

microbiology↗

bioRxiv2020

Nelfinavir inhibits replication of severe acute respiratory syndrome coronavirus 2 in vitro.

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei Province, China. No specific treatment has been established against coronavirus disease-2019 (COVID-19) so far. Therefore, it is urgently needed to identify effective antiviral agents for the treatment of this disease, and several approved drugs such as lopinavir have been evaluated. Here, we report that nelfinavir, an HIV-1 protease inhibitor, potently inhibits replication of SARS-CoV-2. The effective concentrations for 50% and 90% inhibition (EC50 and EC90) of nelfinavir were 1.13 {micro}M and 1.76 {micro}M respectively, the lowest of the nine HIV-1 protease inhibitors including lopinavir. The trough and peak serum concentrations of nelfinavir were three to six times higher than EC50 of this drug. These results suggest that nelfinavir is a potential candidate drug for the treatment of COVID-19 and should be assessed in patients with COVID-19.

microbiology↗

bioRxiv2020

The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15

Steroid compounds, which are expected to have dual functions in blocking host inflammation and MERS-CoV replication, were screened from a chemical library. Within this library, ciclesonide, an inhaled corticosteroid, suppressed human coronavirus replication in cultured cells, but did not suppress replication of respiratory syncytial virus or influenza virus. The effective concentration of ciclesonide to block SARS-CoV-2 (the cause of COVID-19) replication (EC90) was 6.3 M. After the eleventh consecutive MERS-CoV passage in the presence of ciclesonide, a resistant mutation was generated, which resulted in an amino acid substitution (A25V) in nonstructural protein (NSP) 15, as identified using reverse genetics. A recombinant virus with the mutation was also resistant to ciclesonide suppression of viral replication. These observations suggest that the effect of ciclesonide was specific to coronavirus, suggesting this is a candidate drug for treatment of patients suffering MERS or COVID-19.

microbiology↗