Biology subjects

Kato, E.

Publications and source records attributed to Kato, E..

7 recordsLinked to original sources

bioRxiv2026

Differential physiological, behavioral, and medial prefrontal cortex transcriptomic responses to chronic restraint stress between BALB/c and C57BL/6J mice

Chronic stress is a major risk factor for psychiatric disorders such as depression and anxiety, yet the biological basis of individual differences in stress susceptibility and resilience remains poorly understood. Here, we examined physiological, behavioral, and medial prefrontal cortex (mPFC) transcriptomic responses to chronic restraint stress (CRS) in male BALB/c and C57BL/6J mice. After 21 days of CRS, BALB/c mice exhibited greater stress-related changes than C57BL/6J mice, including greater body weight loss, elevated serum corticosterone, reduced serum antioxidant capacity, and more pronounced depression-like behaviors. RNA sequencing showed largely strain-specific transcriptional changes in the mPFC. Strain x stress interaction analysis, followed by canonical pathway analysis using Ingenuity Pathway Analysis (IPA), identified strain-dependent molecular signatures. The most prominent differences involved extracellular matrix (ECM) organization and remodeling and neuroinflammatory signaling pathways, with greater predicted activation in BALB/c mice. IPA upstream regulator analysis further predicted multiple candidate regulators associated with these pathways, including TGF-{beta}/SMAD, C4a/C4b, and MAPK14. Among genes associated with these pathways, several ECM-related genes were preferentially upregulated in BALB/c mice, whereas activity-dependent immediate early genes were preferentially downregulated in C57BL/6J mice. These findings suggest that the strain-dependent mPFC transcriptional programs identified here may contribute to differential stress susceptibility and resilience.

neuroscience↗

bioRxiv2026

The metabolic reprogramming of T cells controls airway remodeling in severe asthma

Mixed granulocytic asthma (MGA) is a severe Th2-low endotype, characterized by high Th17/neutrophilic burden and exacerbated airway remodeling. Both features confer resistance to inhaled corticosteroids, and typical asthma treatments. Thus, MGA is an enormous public health burden. Gaps in knowledge include how Th17 cells induce pathological tissue remodeling, and how Th17 differentiation occurs in response to allergens. We generated a Th2-low murine model of asthma that recapitulates major features of human MGA namely, heightened airway reactivity to methacholine, Th17/neutrophilic inflammation, airway remodeling, and resistance to corticosteroid treatment. Two specific biomarkers enriched in human MGA, the TNF superfamily member 14 (aka LIGHT), and the mitochondrial oxidative phosphorylation (OXPHOS) pathway, are upregulated in this model. We show OXPHOS promotes the metabolic reprograming of Th17 cells, to produce LIGHT that controls airway remodeling. Mechanistically, OXPHOS regulates ROR{gamma}t expression and the subsequent transcriptional network to program survival and differentiation of Th17 cells, whereas LIGHT drives airway remodeling by activating the MMP9-dependent TGF{beta} pathway. Additionally, OXPHOS+Th17 cells promote the expression of osteopontin necessary for fibroblast activation. LIGHT antagonistic blockade reduces airway remodeling, whereas OXPHOS chemical inhibition reduces Th17 cells and neutrophilia. Importantly, the dual blockade of LIGHT and OXPHOS reverses all features of MGA and reciprocally increase the numbers of Treg cells. Thus, the dual blockade of LIGHT and OXPHOS constitutes a promising target for clinical interventions in human MGA, possibly extending to other Th17-driven fibrotic diseases.

immunology↗

bioRxiv2025

Intrathecal administration of palmitoyl-lysophosphatidylethanolamine reduces secondary injury and improves locomotor recovery following spinal cord injury

Spinal cord injury (SCI) triggers secondary pathophysiological cascades, including glutamate excitotoxicity, that result in neuronal loss and impair functional recovery. We have previously shown that lysophosphatidylethanolamine (LPE), a lysophospholipid, promotes neurite outgrowth and protects against glutamate excitotoxicity in cultured cortical neurons. However, whether these effects extend to spinal cord neurons and occur in vivo has remained unclear. In this study, we compared the effects of different LPE species: myristoyl-LPE (14:0 LPE), palmitoyl-LPE (16:0 LPE), stearoyl-LPE (18:0 LPE), and oleoyl-LPE (18:1 LPE) in cultured spinal commissural neurons, and evaluated their effects in vivo using a mouse model of SCI. In cultured neurons, all LPE species promoted neurite outgrowth. Although several species demonstrated a tendency toward neuroprotection, only 16:0 LPE exhibited a statistically significant protective effect against glutamate-induced excitotoxic cell death. Intrathecal administration of 16:0 LPE after SCI reduced TUNEL-positive cells in the acute phase and attenuated lesion expansion at 8 weeks post-injury. Moreover, 5-HT fluorescence intensity was increased in 16:0 LPE-treated mice, suggesting enhanced serotonergic innervation. Furthermore, administration of 16:0 LPE after SCI significantly improved hind-limb motor performance compared with vehicle controls, as assessed by the Basso Mouse Scale. Collectively, these findings suggest that intrathecal administration of 16:0 LPE reduces secondary injury and promotes functional recovery following SCI. Our findings highlight its potential as a therapeutic candidate for SCI.

neuroscience↗

bioRxiv2025

Differential Effects of Inducible Cerebellar Granule Cell and Purkinje Cell Ablation on Motor Coordination and Motor Learning in Adult Mice

The cerebellum regulates motor coordination and motor learning through highly organized circuits composed mainly of granule cells (GCs) and Purkinje cells (PCs). To investigate their distinct roles, we generated two lines of inducible transgenic mice in which either GCs or PCs could be selectively ablated in adulthood by administration of the progesterone receptor antagonist RU-486. This system combined a Cre recombinase-progesterone receptor fusion, in which Cre activity is induced in an RU-486-dependent manner, with a Cre-dependent diphtheria toxin A expression to achieve cell-type-specific ablation. High-dose RU-486 induced nearly complete loss of either GCs or PCs and resulted in severe ataxia. When partial ablation was induced by low-dose RU-486, different phenotypes emerged. Mice retaining about 20% of PCs were still able to improve motor coordination in the rotarod test and maintained performance in the balance beam test comparable to that of controls. In contrast, mice with about 30% of GCs remaining showed marked deficits, failing to improve across rotarod trials and exhibiting reduced latency to fall in the balance beam test. These results suggest that while both GCs and PCs are indispensable for motor coordination, a sufficient number of GCs is required for both motor coordination and motor learning. This inducible ablation model highlights the differential contributions of cerebellar neurons and provides a valuable tool to dissect circuit-specific functions in the adult brain.

neuroscience↗

bioRxiv2025

Diagnosing linearity along the carbon cascade in terrestrial biosphere models

Elevated carbon dioxide (eCO2) fertilises photosynthesis, driving an increase in terrestrial gross primary production (GPP). However, it is unclear how effectively increased GPP propagates along the "carbon (C) cascade" to increase net primary production (NPP) and vegetation C stocks (Cveg) in different plant compartments. Vegetation models simulate divergent C cycle projections and have been criticised for being overly photosynthesis-driven (source-driven), neglecting processes that lead to non-linear behaviour in response to the GPP increase, which may attenuate (or amplify) changes in NPP and vegetation C stocks. Here, we introduce an analytical framework to diagnose linearity (L) of the land C cycle as the ratio of relative changes in linked fluxes and pools and apply it to outputs from 16 models of the TRENDY v11 ensemble. We found widely varying patterns in L across models and for the different links. Six models showed a clear dominance of larger relative changes in NPP than in GPP in global simulations (LNPP:GPP >1 for >60% of gridcells), indicating increased carbon use efficiency under eCO2. Only three models had LNPP:GPP < 1 for >60% of gridcells. Four models showed a clear dominance of larger relative changes in steady-state Cveg than in NPP, while five models showed an opposite pattern - in both cases with a large spread of LCveg*:NPP across gridcells within models. Three models showed a larger relative increase in root C than in Cveg, while two models showed a clear dominance of the opposite pattern. Widely differing distributions of L across models and links reveal a strong influence of alternative process representations (nonlinear behaviour) in individual models. However, for all links, L deviations from 1 were roughly balanced across the model ensemble, leading to an overall linear behaviour of terrestrial C cycle representations.

ecology↗

bioRxiv2025

A scalable framework for current steering at single-neuron resolution

Electrical stimulation at cellular resolution to restore the function of neural circuits is limited by the density of available electrode arrays. Although current steering with multi-electrode stimulation can be used to target cells between electrodes, it has not been proven for systematically targeting individual cells. We develop a framework for cellular-resolution current steering, leveraging the biophysics of electrically-evoked spike generation, and test its efficacy in isolated macaque and human retina. Currents were passed through three electrodes simultaneously using large-scale high-density microelectrode arrays, directly evoking single spikes in retinal ganglion cells. The currents combined either linearly or nonlinearly to drive spiking, depending on the geometry of the electrodes relative to the cell. These findings were captured by a biophysical model and by a simpler parametric model in which spikes can initiate at several sites on the cell membrane, and were leveraged to efficiently identify multi-electrode stimulation patterns that optimized cellular selectivity.

bioengineering↗

bioRxiv2021

In planta genome editing with CRISPR/Cas9 ribonucleoproteins

In planta genome editing represents an attractive approach to engineering crops/varieties that are recalcitrant to culture-based transformation methods. Here, we report the direct delivery of CRISPR/Cas9 ribonucleoproteins into the shoot apical meristem using in planta particle bombardment and introduction of a semidwarf1 (sd1)-orthologous mutation into wheat. The triple knockout tasd1 mutant of an elite wheat variety reduced culm length by 10% without a reduction in yield.

plant biology↗