Biology subjects

Mabuchi, Y.

Publications and source records attributed to Mabuchi, Y..

7 recordsLinked to original sources

bioRxiv2025

Leveraging the salivary microbiome profile to stratify REM sleep behavior disorder and synucleinopathies

Few studies have explored noninvasive biomarkers of synucleinopathies, including Parkinsons disease (PD), and rapid-eye-movement behavior disorder (RBD), a prodromal stage for these conditions. Human oral/salivary microbiomes are altered in PD, highlighting their potential role in both PD pathogenesis and diagnosis. We analyzed 249 salivary microbiomes of controls and patients with idiopathic RBD and various synucleinopathies, including two subgroups divided based on the presence of RBD symptoms, through both cross-sectional and longitudinal studies. The microbiome composition was strikingly similar between patients with RBD and early PD exhibiting RBD symptoms. The area under the curve range for distinguishing RBD from controls and each synucleinopathy was 0.85-0.94. We further performed pseudotime trajectory analysis of the microbiome compositional space; populations with low diversity, enriched Streptococcus, and depleted Neisseria exhibited a brief pseudotime transition from RBD to early PD. Our findings suggest that early PD-like salivary dysbiosis manifests during RBD, allowing for the stratification of synucleinopathies through the innovative use of salivary microbiome profiles.

neuroscience↗

bioRxiv2025

Social experience alters behaviors by reprogramming the Fruitless pathway and circadian state in Drosophila

From flies to humans, social experience affects various cognitive and behavioral processes. Previous studies have shown that group housing suppresses many behaviors like courtship, aggression, and feeding in Drosophila melanogaster, in addition to resetting the circadian state. Here, we focus on group housing-induced courtship suppression. To determine the mechanisms by which social experience modulates courtship behaviors, we performed bulk tissue RNAseq and single-cell RNAseq from cells expressing FruitlessM (FruM) and DoublesexM (DsxM), two transcription factors that label interconnected neural circuits for socially driven behaviors, from grouped or isolated male brains. These revealed that social isolation alters fru and dsx levels throughout the brain. Knocking down fruM in different fruM-positive neuron subpopulations in the brains has diverse effects on social experience-dependent changes in courtship. Furthermore, group housing increases the expression of stripe (sr) and Hormone receptor-like in 38 (Hr38) genes encoding neural activity-induced transcription factors in most neurons within social circuits. We found that knocking down sr in fruM-positive neurons effectively eliminates the impact of social experience by increasing courtship in group-housed males. Importantly, social experience also alters the expression of FruM/DsxM putative target genes regulating circadian states throughout the brain. Disrupting the function of multiple circadian genes diminishes the effect of group housing on courtship. Our findings suggest that group housing/social enrichment suppresses courtship by reprogramming the circadian arousal state, whereas courtship-elevating effects of social experience rely on unique influences of FruM expression and function in different neurons within social and clock circuits. These results are significant as they point to modulation of circadian arousal state as a possible central strategy for mediating the pleiotropic effects of social experience on organismal responses.

neuroscience↗

bioRxiv2025

A bright synthetic near-infrared luciferin enhances the capabilities of deep-tissue bioluminescence imaging using firefly luciferases

Synthetic bioluminescence reactions exhibiting near-infrared (NIR)-shifted spectra have been explored to improve deep-tissue imaging through the design of firefly luciferin analogues. Although the NIR bioluminescence reactions improve the tissue penetration of bioluminescence signals from deep tissues, their photon output is markedly lower compared to the natural reaction with D-luciferin and firefly luciferase (Fluc), often by an order of magnitude or more. Consequently, in most instances, the sensitivity of NIR bioluminescence imaging (NIR-BLI) has not yet substantially surpassed that of BLI with the natural firefly reaction. Here, we present a synthetic firefly luciferin, named AkaSuke, that generates intense NIR bioluminescence ({lambda}max = 680 nm) in reaction with Fluc, greatly improving the detection sensitivity beyond that of the D-luciferin/Fluc reaction for targeting deep tissue. AkaSuke enables sensitive visualizations of ectopic hematogenesis through entire tissues of mice over time following transplantation of bone marrow stem cells labeled with Fluc. We additionally identify a Japanese firefly luciferase, DkumLuc1, that displays higher catalytic activities for bioluminescence emission of AkaSuke compared to typical Fluc, resulting in detection sensitivity comparable to that of AkaLumine/Akaluc reaction, one of the most sensitive bioluminescence systems for deep tissue imaging. We further propose the potential of the AkaSuke/DkumLuc1 reaction as an orthogonal pair with the AkaLumine/Akaluc for sensitive dual-target tracking in mice. Overall results suggest that AkaSuke enhances the capabilities of deep-tissue bioluminescence imaging using Fluc and its variant, and could serve as an emerging benchmark for the molecular design of NIR luciferin analogues.

cancer biology↗

bioRxiv2024

Differentiation of Mesenchymal Stem/ Stromal Cells into CD45+ Macrophage-like Cells: Expanding Insights into MSC Plasticity

Mesenchymal stem/stromal cells (MSCs) are notable for their differentiation potential and immunomodulatory properties. They share several features with macrophages that are also similar to those of fibrocytes. This study aimed to investigate the relationship between MSCs, fibrocytes, and macrophages, focusing on the hypothesis of a possible direct lineage. This study focuses on a freshly isolated murine MSC population known as PSmMSCs (CD45- TER119- Sca-1+ PDGFR+). Transplanting PSmMSCs from transgenic GFP mice into irradiated recipients produced GFP+ cells expressing the macrophage markers CD45, CD68, and CD115, indicating a macrophage-like phenotype. Further analysis showed that PSmMSCs cultured in macrophage differentiation media acquired characteristics of M2 macrophages (CD45, CD68, and CD206). These results were confirmed in two different mouse strains as well as in human MSCs (hMSCs). Single-cell RNA sequencing revealed macrophage-like and fibrocyte-like populations among the PSmMSCs. These findings demonstrate the phenotypic plasticity of freshly isolated MSCs to transition into macrophage-like and/or fibrocyte-like states, which has not been reported, particularly in long-term cultured MSCs. This study provides new insights into MSC plasticity and its potential roles in immune regulation and tissue repair.

cell biology↗

bioRxiv2023

Connection between drug-mediated neurotransmission and salivary microbiome

Salivary microbiome alterations associated with cognitive function have been reported in patients with neurodegenerative diseases1-3. Gut microorganisms can modulate therapeutic efficacy via drug metabolism4-7. Additionally, several drugs against diabetes and inflammatory bowel disease can lead to microbial dysbiosis8-10. However, the effect of central nervous system (CNS) drug use on the microbiome remains unknown. Here, we show that the usage of anti-dementia drugs, including donepezil and memantine, more largely affects the salivary microbiome composition than the gut microbiome composition. We observed salivary microbiome diversity reduction in patients with neurodegenerative diseases who received N-methyl-D-aspartate receptor inhibitor drugs. Furthermore, the use of acetylcholine-modulating drugs contributed to the salivary microbiome composition, suggesting that the salivary microbiome responds to changes in CNS drug-induced cerebral acetylcholine and glutamate levels. Multivariate analysis adjusted with or without the use of anti-dementia drugs demonstrated that the difference in the salivary microbiome correlated with cognitive function. We show the unique salivary microbiome structure of CNS drug users, suggesting the possibility of monitoring pharmacokinetics using the salivary microbiome. Our results also provide evidence of the presence of the microbiome-oral-brain axis and will accelerate the elucidation of the interplay between the salivary microbiome and neurodegeneration.

microbiology↗

bioRxiv2023

GABA-mediated inhibition in visual feedback neurons fine-tunes Drosophila male courtship

Vision is critical for the regulation of mating behaviors in many species. Here, we discovered that the Drosophila ortholog of human GABAA-receptor-associated protein (GABARAP) is required to fine-tune male courtship by modulating the activity of visual feedback neurons, lamina tangential cells (Lat). GABARAP is a ubiquitin-like protein that regulates cell-surface levels of GABAA receptors. Knocking down GABARAP or GABAA receptors in Lat neurons or hyperactivating them induces male courtship toward other males. Inhibiting Lat neurons, on the other hand, delays copulation by impairing the ability of males to follow females. Remarkably, the human ortholog of Drosophila GABARAP restores function in Lat neurons. Using in vivo two-photon imaging and optogenetics, we show that Lat neurons are functionally connected to neural circuits that mediate visually-guided courtship pursuits in males. Our work reveals a novel physiological role for GABARAP in fine-tuning the activity of a visual circuit that tracks a mating partner during courtship.

neuroscience↗

bioRxiv2022

CD73-positive cell spheroid transplantation attenuates colonic atrophy

The incidence of inflammatory bowel diseases (IBD) is increasing worldwide. Mesenchymal stem/stromal cells (MSCs) have immunomodulatory functions and are a promising source for cell transplantation therapy for IBD. However, owing to their heterogeneous nature, their therapeutic efficacy in colitis is controversial and depends on the delivery route and form of transplanted cells. Cluster of differentiation (CD)73 is widely expressed in MSCs and used to obtain a homogeneous MSC population. Herein, we determined the optimal method for MSC transplantation using CD73+ cells in a colitis model. mRNA sequencing analysis showed that CD73+ cells exhibit downregulation of inflammatory genes and upregulation of extracellular matrix-related genes. Furthermore, three-dimensional CD73+ cell spheroids showed enhanced engraftment at the injured site through the enteral route, facilitated extracellular matrix remodeling, and downregulated inflammatory gene expression in fibroblasts, leading to attenuation of colonic atrophy. Therefore, the interaction between intestinal fibroblasts and exogenous MSCs via tissue remodeling is one mechanism that can be exploited for colitis prevention. Our results highlight that transplantation of homogeneous cell populations with well-characterized properties is beneficial for IBD treatment.

cell biology↗