Biology subjects

Okabe, S.

Publications and source records attributed to Okabe, S..

11 recordsLinked to original sources

bioRxiv2026

BMP4 Restricts Axonal Ramification and Bouton Density in Cholinergic Projections from the Basal Forebrain

Axonal projections and precise synapse formation are essential for the establishment of functional neural circuits, and their dysregulation contributes to various psychiatric and neurodegenerative disorders. Although numerous extracellular cues secreted from surrounding tissues regulate axon guidance and synapse formation, the mechanisms by which neurons locally regulate terminal patterning within their projection fields remain poorly understood. Bone morphogenetic protein 4 (BMP4) is a classical morphogen that is involved in early neural tube patterning during development. However, its postnatal function remains unclear. Previous in vitro studies using hippocampal glutamatergic neurons demonstrated that BMP4 can act locally on axons to suppress synapse formation, raising the possibility that BMP4 regulates terminal differentiation after target innervation. Here, we investigated the role of BMP4 in postnatal cholinergic circuit development using cholinergic neuron-specific Bmp4 conditional knockout (Bmp4 cKO) mice, with adult analyses performed in males. Basal forebrain cholinergic neurons project extensively throughout the neocortex and are essential for higher brain functions, including arousal and attention. Bmp4 cKO mice exhibited increased cholinergic axon terminals in the neocortex, hippocampus, and amygdala, as well as increased axonal ramification in the neocortex without affecting cytoarchitectonic organization or cholinergic neuron numbers in the basal forebrain. These findings demonstrate that BMP4 functions as a negative regulator of cholinergic terminal formation and axonal arborization, suggesting that BMP4 may act locally to restrict cholinergic axonal expansion during neural circuit maturation.

neuroscience↗

bioRxiv2026

Hydrogel-enhanced bioelectrochemical nitrate reduction for ammonium recovery from dilute nitrate via Shewanella oneidensis MR-1

Bioelectrochemical reduction of dilute nitrate (NO-; sub-mM to low-mM range) to ammonium (NH) offers a promising route toward circular nitrogen management from contaminated groundwater and environmental waters. However, on-site application of bioelectrochemical systems remains challenging due to low reduction rates and poor electron transfer efficiency of naturally formed biofilm electrodes. Here, we constructed a hydrogel biocathode by applying a carbon black/riboflavin/sodium alginate/cellulose hydrogel incorporating Shewanella oneidensis MR-1 cells to a graphite felt electrode via brush coating. The hydrogel electrode achieved NH production rates of 0.16-0.19 mol m-3 h-{superscript 1} without NO2- accumulation, and these rates were maintained without significant performance loss across three consecutive cycles with medium exchange over 1.5 days of total operation. The hydrogel electrode increased the current density by more than 5-fold compared with a conventional S. oneidensis biofilm electrode, indicating enhanced electron transfer efficiency per unit biomass, which directly contributed to the high NH production rates. The electricity consumption for NH production of 1.68-2.39 x 10{superscript 2} kJ g-N-{superscript 1} was substantially lower than that of metal catalyst systems at comparable NO- concentrations (typically, >104 kJ g-N-{superscript 1}). These findings demonstrate that the hydrogel electrode design represents an energy-efficient, and readily fabricated platform for bioelectrochemical NH production from dilute NO-.

microbiology↗

bioRxiv2025

Decoding Spine Nanostructure in Mental Disorders Reveals a Schizophrenia-Linked Role for Ecrg4

Dendritic spine dysfunction may contribute to the etiology and symptom expression of neuropsychiatric disorders. The intimate relationship between spine morphology and function suggests that decoding disease-related abnormalities from spine morphology can aid in developing synapse-targeted interventions. Here, we describe a population analysis of dendritic spine nanostructure applied to the objective grouping of multiple mouse models of neuropsychiatric disorders. This method has identified two major groups of spine phenotypes linked to schizophrenia and autism spectrum disorder (ASD). An increase in spine subpopulation with small volumes characterized the spines of schizophrenia-associated mouse models, whereas a spine subset with large volumes increased in ASD models. Schizophrenia-associated mouse models showed higher similarity in spine morphology, driven by reduced size and growth of nascent spines. The expression of Ecrg4, a gene encoding small secretory peptides, was increased in schizophrenia-associated mouse models, and functional studies confirmed its critical involvement in impaired spine dynamics and shape. These results suggest that population-level spine analysis provides rich insights into heterogeneous spine pathology, facilitating the identification of new molecular targets related to core synaptic dysfunction.

neuroscience↗

bioRxiv2025

Intercellular communication in the brain via dendritic nanotubular network

Recent studies have identified intercellular networks for material exchange by bridge-like nanotubular structures, yet their existence in neurons remains unexplored within the brain. Here, we identified long, thin dendritic filopodia that establish direct dendrite-to-dendrite contacts, forming dendritic nanotubes (DNTs) in mammalian brains. Using super-resolution microscopy, we characterized their unique molecular composition and dynamics in dissociated neurons, enabling Ca2+ propagation over distances. Utilizing imaging and machine-learning-based analysis, we confirmed the in situ presence of DNTs connecting dendrites to other dendrites whose anatomical features are distinguished from synaptic dendritic spines. DNTs mediate the active transport of small molecules or human amyloid-beta (A{beta}), implicating the role of DNT network in AD pathology. Notably, DNT levels increased prior to the onset of amyloid plaque deposits in the mPFC of APP/PS1 mice. Computational simulations predicted the progression of amyloidosis, providing insight into the mechanisms underlying neurodegeneration through these DNTs. This study unveils a previously unrecognized nanotubular network, highlighting another dimension of neuronal connectivity beyond synapses.

neuroscience↗

bioRxiv2025

Membrane vesicles of Shewanella oneidensis MR-1 enhance denitrification growth in a species-selective manner

Denitrification, a fundamental bacterial respiratory process that occurs in anoxic environments, plays a pivotal role in energy synthesis and the global nitrogen cycle. Although the significance of this process is well-recognized, its regulation within polymicrobial communities remains poorly understood, particularly concerning interspecies interactions. In this study, we investigated the role that bacterial membrane vesicles (MV) play in modulating denitrification across bacterial species. MV is known to carry specific biomolecules such as secondary metabolites, proteins, and nucleic acids, therefore considered to be a secretion pathway. We found that MV produced by Shewanella oneidensis enhanced denitrification in a species-specific manner. Bacteria with highly hydrophobic surfaces tended to respond to denitrification enhancement, suggesting that the MV-bacteria attachment process is the key to generating species specificity. Transcriptome analysis and isotopic metabolite tracking indicated that the MV influenced denitrifying activities, rather than the transcription of denitrification-related genes. We further demonstrated that c-type cytochromes in MV act as key components that enhance denitrification. These insights expand our understanding of bacterial ecology, highlighting the role of membrane vesicles in facilitating respiratory competition and cooperation in polymicrobial communities.

microbiology↗

bioRxiv2024

Beyond dichotomy: diversity of rat's ultrasonic vocalizations

Rats emit ultrasonic vocalizations (USVs) in diverse contexts, and these USVs are thought to serve many biological functions, such as socio-coordinating and alarming functions. In particular, rat USVs have been established as a good model for studying emotional expressions. Since the discovery of USVs in rats, it has gradually been revealed that two families of juvenile and adult rat USVs with distinct acoustic features are closely linked to different affective states: 50-kHz (high-short) calls are associated with positive affective states, whereas 22-kHz (low-long) calls are associated with negative affective states. Although various subtypes within high-short and low-long calls have been proposed and used, most studies adopt the dichotomous framework of first dividing USVs into high-short or low-long calls. The diversity of rat USVs may have been overlooked due to this high-short / low-long dichotomous framework, as such labeling could discourage reporting of actual measured acoustic properties. Considering that several recent studies claim to have found new USV categories outside this framework, we conducted a systematic survey of descriptions of rat USVs in the literature. We identified 15 articles reporting USVs that are outside the dichotomous framework. Our results support the existence of diverse USVs beyond the dichotomy, highlighting the importance of research on a broader range of vocalizations that might reflect complex affective states beyond the simple distinction between positive and negative.

animal behavior and cognition↗

bioRxiv2022

Rats emit unique distress calls in social inequality conditions

Humans show aversion toward inequality of social reward, and this aversion plays important roles for the establishment of social cooperation. However, it has remained unknown whether commonly used experimental animals show negative responses to social reward inequality. In this study, we found that rats showed bonding-like behavior to an affiliative human who repeatedly stroked the rats. In addition, these rats emitted distress calls, an index of negative emotion, when an affiliative human stroked another rat in front of them. These distress calls had acoustic characteristics different from those emitted in response to physical stress stimuli such as air-puff. Rats emitted calls with higher frequency (28 kHz) and shorter durations (0.05 sec) in an inequality condition than the frequency and durations of calls emitted when receiving air-puff. Our results suggested that rats exhibited negative emotion with unique distress calls in response to a social inequality condition.

animal behavior and cognition↗

bioRxiv2021

Dynamics of peripheral blood flow across sleep stages

Study ObjectivesPulse rate variability (PRV) derived from peripheral blood flow has been reported as a surrogate parameter for heart rate variability (HRV). However, there are currently no studies reporting systematic comparisons of PRV with HRV in a normal sleep state. Whether PRV can provide similar information regarding sleep stages remains unclear. Peripheral blood flow may also be modulated differently across sleep stages. Thus, we aimed to investigate blood flow dynamics and compare PRV with HRV across sleep stages to see if blood flow can provide further information about sleep stages. MethodsWe performed electrocardiography and simultaneously measured blood flow from the right index finger and ear concha of 45 healthy participants (13 women; mean age, 22.5 {+/-} 3.4 years) during one night of sleep. Time-domain, frequency-domain, and non-linear indices of PRV/HRV, and time- and frequencydomain blood flow parameters were calculated. ResultsFinger-PRV results showed similar patterns to HRV results for most parameters. Finger-blood flow parameters in the time and frequency domains also showed information about the different sleep stages. Further, both finger- and ear-blood flow results showed 0.2-0.3 Hz oscillations that varied with sleep stages, with a significant increase in N3, suggesting a modulation (of respiration) within this frequency band. ConclusionsThese results suggest that PRV can provide as much information as HRV for different sleep stages. Furthermore, the results show that blood flow + PRV could be more advantageous than HRV alone in the assessment of the sleep state and related autonomic nervous activity. Statement of SignificanceThe research provides comprehensive information on peripheral blood flow (BF) activity across sleep stages for the first time, as the major novelty of our work. The second contribution is a systematic study comparing BF-derived pulse rate variability (PRV) with heart rate variability across sleep stages in a normal sleep state. We believe that our work makes a significant contribution to the literature because it provides comprehensive information on the potential of BF+PRV as a new biomarker for assessing the sleep state. Further, this study contributes to developing a more convenient method of assessing the sleep state in the clinical and home/work setting.

physiology↗

bioRxiv2021

Systematic analysis of brain lactate and pH levels in 65 animal models related to neuropsychiatric conditions

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2,294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimers disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.

neuroscience↗

bioRxiv2019

Bottleneck Size-Dependent Changes in the Genetic Diversity and Specific Growth Rate of a Rotavirus A Strain

RNA viruses form a dynamic distribution of mutant swarm (termed \"quasispecies\") due to the accumulation of mutations in the viral genome. The genetic diversity of a viral population is affected by several factors, including a bottleneck effect. Human-to-human transmission ex-emplifies a bottleneck effect in that only part of a viral population can reach the next susceptible hosts. In the present study, the rhesus rotavirus (RRV) strain of Rotavirus A was serially passaged five times at a multiplicity of infection (MOI) of 0.1 or 0.001 in duplicate (the 1st and 2nd lineages), and three phenotypes (infectious titer, cell binding ability and specific growth rate) were used to evaluate the impact of a bottleneck effect on the RRV population. The specific growth rate values of lineages passaged under the stronger bottleneck (MOI of 0.001) were higher after five passages. The nucleotide diversity also increased, which indicated that the mutant swarms of the lineages under the stronger bottleneck effect were expanded through the serial passages. The random distribution of synonymous and non-synonymous substitutions on rotaviral genome segments indicated that almost all mutations were selectively neutral. Simple simulations revealed that the presence of minor mutants could influence the specific growth rate of a population in a mutant frequency-dependent manner. These results indicate that a stronger bottleneck effect can create more sequence spaces for minor mutants originally existing in a hidden layer of mutant swarm.\n\nIMPORTANCEIn this study, we investigated a bottleneck effect on an RRV population, which may drastically impact a viral population structure. RRV populations were serially passaged under two levels of a bottleneck effect, which exemplified a human-to-human transmission. As a result, the genetic diversity and specific growth rate of RRV populations increased under the stronger bottleneck effect, which implied that a bottleneck could create a new sequence space in a population for minor mutants originally existing in a hidden layer of a mutant swarm of the double-stranded RNA virus. The results of this study suggest that the genetic drift caused by a bottleneck in a human-to-human transmission explains the random appearance of new genetic lineages causing viral outbreaks, which can be expected by the molecular epidemiology using next generation sequencing in which the viral genetic diversity within a viral population is investigated.

microbiology↗

bioRxiv2019

USVSEG: A robust segmentation of rodents’ ultrasonic vocalization

Rodents ultrasonic vocalization (USV) provides useful information to assess their social behaviors. Despite of previous efforts for classifying subcategories of time-frequency patterns of USV syllables to associate with their functional relevances, detection of vocal elements from continuously recorded data have remained to be not well-optimized. We here propose a novel procedure for detecting USV segments in continuous sound data with background noises which were inevitably contaminated during observation of the social behavior. The proposed procedure utilizes a stable version of spectrogram and additional signal processing for better separation of vocal signals by reducing variation of the background noise. Our procedure also provides a precise time tracking of spectral peaks within each syllable. We showed that this procedure can be applied to a variety of USVs obtained from several rodent species. A performance test with an appropriate parameter set showed performance for detecting USV syllables than conventional methods.

animal behavior and cognition↗