Biology subjects

Homma, S.

Publications and source records attributed to Homma, S..

7 recordsLinked to original sources

bioRxiv2026

Postmortem Alterations of Metabotropic Glutamate Receptors across Neuropsychiatric Disorders: A Systematic Review

Metabotropic glutamate receptors (mGluRs) regulate glutamatergic transmission and have been implicated in diverse neuropsychiatric disorders, but human postmortem evidence remains fragmented. We aimed to map these findings across diagnoses, receptor subtypes, brain regions, and measurement modalities. Following PRISMA guidelines, we systematically searched MEDLINE, EMBASE, and Web of Science from inception to August 8, 2026, for studies assessing GRM transcripts, as well as mGluR protein abundance, localization, assembly, or receptor binding in human postmortem brain tissue. Of 532 records identified, 57 reports met eligibility criteria. Findings were synthesized narratively because of substantial heterogeneity in diagnoses, brain regions, receptor subtypes, and assays. Postmortem evidence was concentrated on mGluR5, mGluR2/3, and mGluR1, and on the prefrontal cortex, anterior cingulate cortex, and hippocampus. mGluR-related alterations were reported across disorders, including schizophrenia, major depressive disorder, Alzheimer disease, autism spectrum disorder, and alcohol use disorder. Although most analyses yielded null findings, the direction and magnitude of mGluR alterations varied across brain regions, receptor subtypes, and molecular endpoints. This inconsistency may partly reflect the distinct biological levels captured by transcript abundance, total protein, receptor assembly, localization, and ligand binding, together with regional, cell-type, disease-stage, and clinical heterogeneity. The available evidence therefore suggests context-dependent alterations in mGluR biology but not a uniform or disorder-specific molecular signature. Integration of postmortem findings with other approaches, including in vivo imaging, may clarify their biological and clinical significance.

neuroscience↗

bioRxiv2026

Modulating supplementary motor area excitability enhances groove-related pleasure during music listening

Pleasurable urge to move to music is often referred to as groove. Although previous studies have shown an association between the supplementary motor area (SMA) and the groove experience, its causal role remains unclear. Here, we investigated whether the SMA is causally involved in groove experience during music listening using repetitive transcranial magnetic stimulation. Fifteen healthy participants completed three sessions on separate days: excitatory stimulation (intermittent theta burst stimulation; iTBS) over the SMA, inhibitory stimulation (continuous theta burst stimulation; cTBS) over the SMA, and sham stimulation (iTBS or cTBS) over the vertex. After each stimulation session, participants listened to five high-groove and five low-groove musical excerpts and rated urge-to-move and pleasure on a 0-100 scale. Heart rate was additionally recorded as an exploratory physiological measure during music listening. Linear mixed-effects models (LMM) showed that pleasure ratings, but not urge-to-move ratings, were higher following both iTBS and cTBS compared with sham stimulation. In exploratory LMMs, reduced log-transformed heart rate variability (HRV) significantly predicted higher pleasure ratings. These findings suggest that SMA stimulation modulates the pleasurable component of the groove experience, likely via network-level mechanisms rather than a simple linear relationship between SMA excitability and pleasure. They also raise the possibility that reduced parasympathetic activity, reflected by lower HRV, mediates the stimulation-related increase in musical pleasure. Future studies should investigate the causal roles of other brain regions as well as clarify the directionality between autonomic changes and the groove experience.

neuroscience↗

bioRxiv2025

Pleasure in groove is associated with neuromelanin levels in the substantia nigra of younger healthy individuals: A neuromelanin-sensitive MRI study

The pleasurable urge to move in response to music is called groove. Prior research has suggested a potential link between groove and dopamine function. However, no studies to date have directly investigated the relationship between the two. Here, we aimed to assess individual dopamine function in the substantia nigra of healthy individuals using neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a non-invasive method associated with dopamine function, and to investigate the relationship between the individual dopamine proxy index and sensitivity to the groove experience. In this study, 15 younger (< 48 years) and 16 older ([greater double equals]48 years) healthy individuals participated. Participants listened to ten musical excerpts and rated the groove experience based on "pleasure" and "wanting to move." To assess whether the groove experience is related to NM levels, type of musical excerpts, and sex, we analyzed with linear mixed-effects regression models. The results showed that higher NM levels (p = 0.032) and male sex (p = 0.034) were associated with higher pleasure ratings in the younger group. For the "urge to move" ratings, type of musical excerpts was associated with ratings in both groups (ps < 0.001), where high-groove music (Janata et al., 2012) receiving higher ratings. Taken together, these results suggest that the "pleasure" aspect of the groove experience in younger individuals was related to dopamine levels in the substantia nigra, but may not be associated with the "urge to move." Thus, pleasure and the urge to move are likely to involve distinct dopaminergic pathways and mechanisms, warranting further investigation.

neuroscience↗

bioRxiv2024

Secreted Particle Information Transfer (SPIT) - A Cellular Platform For In Vivo Genetic Engineering

A multitude of tools now exist that allow us to precisely manipulate the human genome in a myriad of different ways. However, successful delivery of these tools to the cells of human patients remains a major barrier to their clinical implementation. Here we introduce a new cellular approach for in vivo genetic engineering, Secreted Particle Information Transfer (SPIT) that utilizes human cells as delivery vectors for in vivo genetic engineering. We demonstrate the application of SPIT for cell-cell delivery of Cre recombinase and CRISPR-Cas9 enzymes, we show that genetic logic can be incorporated into SPIT and present the first demonstration of human cells as a delivery platform for in vivo genetic engineering in immunocompetent mice. We successfully applied SPIT to genetically modify multiple organs and tissue stem cells in vivo including the liver, spleen, intestines, peripheral blood, and bone marrow. We anticipate that by harnessing the large packaging capacity of a human cells nucleus, the ability of human cells to engraft into patients long term and the capacity of human cells for complex genetic programming, that SPIT will become a paradigm shifting approach for in vivo genetic engineering.

synthetic biology↗

bioRxiv2023

Dual α-globin and truncated erythropoietin receptor knock-in restores hemoglobin production in α-thalassemia major-derived hematopoietic stem and progenitor cells

Alpha-thalassemia is an autosomal recessive disease with increasing worldwide prevalence. The molecular basis is due to mutation or deletion of one or more duplicated -globin genes, and disease severity is directly related to the number of allelic copies compromised. The most severe form, -thalassemia major (TM), results from loss of all four copies of -globin and has historically resulted in fatality in utero. However, in utero transfusions now enable survival to birth. Postnatally, patients face challenges similar to {beta}-thalassemia, including severe anemia and erythrotoxicity due to imbalance of {beta}-globin and -globin chains. While curative, hematopoietic stem cell transplantation (HSCT) is limited by donor availability and potential transplant-related complications. Despite progress in genome editing treatments for {beta}-thalassemia, there is no analogous curative option for patients suffering from -thalassemia. To address this, we designed a novel Cas9/AAV6-mediated genome editing strategy that integrates a functional -globin gene into the {beta}-globin locus in TM patient-derived hematopoietic stem and progenitor cells (HSPCs). Incorporation of a truncated erythropoietin receptor transgene into the -globin integration cassette dramatically increased erythropoietic output from edited HSPCs and led to the most robust production of -globin, and consequently normal hemoglobin. By directing edited HSPCs toward increased production of clinically relevant RBCs instead of other divergent cell types, this approach has the potential to mitigate the limitations of traditional HSCT for the hemoglobinopathies, including low genome editing and low engraftment rates. These findings support development of a definitive ex vivo autologous genome editing strategy that may be curative for -thalassemia. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/555926v2_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1b63dacorg.highwire.dtl.DTLVardef@18b25a1org.highwire.dtl.DTLVardef@53835corg.highwire.dtl.DTLVardef@d52bf5_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2020

Three-Component Model of the Spinal Nerve Branching Pattern, based on the View of the Lateral Somitic Frontier and Experimental Validation

One of the decisive questions about human gross anatomy is unmatching the adult branching pattern of the spinal nerve to the embryonic lineages of the peripheral target muscles. The two principal branches in the adult anatomy, the dorsal and ventral rami of the spinal nerve, innervate the intrinsic back muscles (epaxial muscles), as well as the body wall and appendicular muscles (hypaxial muscles), respectively. However, progenitors from the dorsomedial myotome develop into the back and proximal body wall muscles (primaxial muscles) within the sclerotome-derived connective tissue environment. In contrast, those from the ventrolateral myotome develop into the distal body wall and appendicular muscles (abaxial muscles) within the lateral plate-derived connective tissue environment. Thus, the ventral rami innervate muscles that belong to two different embryonic compartments. Because strict correspondence between an embryonic compartment and its cognate innervation is a way to secure the development of functional neuronal circuits, this mismatch indicates that we may need to reconcile our current understanding of the branching pattern of the spinal nerve with regard to embryonic compartments. Accordingly, we first built a model for the branching pattern of the spinal nerve, based on the primaxial-abaxial distinction, and then validated it using mouse embryos. In our model, we hypothesized the following: 1) a single spinal nerve consists of three nerve components: primaxial compartment-responsible branches, a homologous branch to the canonical intercostal nerve bound for innervation to the abaxial compartment in the ventral body wall, and a novel class of nerves that travel along the lateral cutaneous branch to the appendicles; 2) the three nerve components are discrete only during early embryonic periods but are later modified into the elaborate adult morphology; and 3) each of the three components has its own unique morphology regarding trajectory and innervation targets. Notably, the primaxial compartment-responsible branches from the ventral rami have the same features as the dorsal rami. Under the above assumptions, our model comprehensively describes the logic for innervation patterns when facing the intricate anatomy of the spinal nerve in the human body. In transparent whole-mount specimens of embryonic mouse thoraces, the single thoracic spinal nerve in early developmental periods trifurcated into superficial, deep, and lateral cutaneous branches; however, it later resembled the adult branching pattern by contracting the superficial branch. The superficial branches remained segmental while the other two branches were free from axial restriction. Injection of a tracer into the superficial branches of the intercostal nerve labeled Lhx3-positive motoneurons in the medial portion of the medial motor column (MMCm). However, the injection into the deep branches resulted in retrograde labeling of motoneurons that expressed Oct6 in the lateral portion of the medial motor column (MMCl). Collectively, these observations on the embryonic intercostal nerve support our model that the spinal nerve consists of three distinctive components. We believe that our model provides a framework to conceptualize the innervation pattern of the spinal nerve based on the distinction of embryonic mesoderm compartments. Because such information about the spinal nerves is essential, we further anticipate that our model will provide new insights into a broad range of research fields, from basic to clinical sciences.

developmental biology↗

bioRxiv2020

Senescent cell death as an aging resistance mechanism in naked mole-rat

Naked mole-rats (NMRs) are the longest-lived rodents, showing minimal aging phenotypes. An unsolved paradox is that NMRs exhibit low intracellular anti-oxidant defence despite minimal aging. Here, we explained a link between these “contradicting” features by a phenomenon termed “senescent cell death (SCD)”—Senescence induced cell death in NMR cells due to their inherent vulnerability to reactive oxygen species and unique metabolic system. In NMR skin, we observed few senescent cells during aging or after ultraviolet irradiation, suggesting suppression of senescent cell accumulation in NMR tissue. We discovered that senescent NMR-fibroblasts induce SCD through retinoblastoma protein activation accompanied by autophagy dysregulation, increased oxidative damage and accelerated H2O2-releasing metabolic pathways. During senescence, NMR cells showed resistance to metabolic remodelling unlike mice. Our findings provide mechanistic insights into how extraordinary aging resistance is accomplished in NMR. This will contribute to the development of senolytic drugs to regulate age-related diseases.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cell biology↗