Biology subjects

Oishi, H.

Publications and source records attributed to Oishi, H..

6 recordsLinked to original sources

bioRxiv2025

Metabolic organization of macaque visual cortex reflects retinotopic eccentricity and category selectivity

Neural activity requires energy metabolism, and the brains metabolic architecture varies across regions. Yet, it remains unclear whether these variations are meaningfully related to the functional and perceptual demands of cortical processing. In high-level visual cortex, category-selective regions, such as those preferentially responding to faces and scenes, are consistently distributed along a topographic axis that varies in sensitivity to spatial scale, a feature dimension that imposes differing metabolic demands at the level of the retina. This axis reflects a broader organizing principle of the visual system: retinotopic eccentricity, the topographic mapping of visual space relative to gaze. Here, we tested whether cortical metabolic architecture reflects this principle by aligning in vivo fMRI maps of eccentricity and visual category selectivity with ex vivo cytochrome oxidase (CO) histology, a marker of oxidative metabolism, in macaque visual cortex. We found that face-selective region ML, which is biased toward central vision, exhibits higher CO intensity than the peripherally-biased scene-selective region LPP. More broadly, CO intensity covaries with eccentricity across the entire occipitotemporal cortex, though this gradient only partially accounts for the elevated CO in ML. These findings reveal a close correspondence between cortical energy consumption and retinotopic representation, suggesting that metabolic resources are shaped by the processing demands of visual perception.

neuroscience↗

bioRxiv2023

CTRP7 as a Molecular Biomarker for Predicting Responsiveness to Pulmonary Vasodilators: Insights from Human and Animal Studies in Pulmonary Arterial Hypertension

BackgroundPulmonary arterial hypertension (PAH) is a life-threatening condition. Although pulmonary vasodilators have shown promise in managing PAH, the overall prognosis improvement is modest, partly because of the absence of a biomarker for guiding their selection. This study aimed to identify the molecular-based predictors of responsiveness to pulmonary vasodilators by combining human and basic studies. Methods and ResultsRNA sequencing was conducted on cultured pulmonary artery smooth muscle cells (PASMCs) from patients with and without PAH, identifying variations in 2,076 genes. The candidates were narrowed down to established clinical biomarkers, and their plasma levels were assessed in PAH (n = 123) and non-PAH patients (n = 25). C1q/TNF-related protein 7 (CTRP7) exhibited elevated expression in PASMCs (5.37 Log2 fold change, p < 0.01), and the plasma of patients with PAH compared to non-PAH (28.2 (9.3- 101.2) vs. 9.32 (4.6-18.6) ng/ml, p < 0.01). A plasma assessment revealed a significant correlation between CTRP7 and interleukin 6 (IL-6) levels (r = 0.544, p < 0.001). Chromatin immunoprecipitation demonstrated that IL-6 upregulated CTRP7 expression in PASMCs. Among pivotal factors, CTRP7 reduced prostacyclin analog receptor (PTGIR) expression through Rab5a-mediated internalization, resulting in diminished responsiveness to selexipag (a prostacyclin analog). Incorporating the human study, hypoxic PH mice demonstrated reduced PTGIR expression in the pulmonary arteries, which correlated with limited responses to selexipag treatment (low cardiac output and persistent pulmonary artery resistance), which was mitigated by silencing CTRP7 expression in the pulmonary arteries using adeno-associated virus 6. ConclusionsAmong the candidates with increased expression in patients with PAH based on RNA sequencing of PASMCs, CTRP7 demonstrated elevated plasma levels compared to non-PAH. CTRP7 regulated PTGIR internalization via inflammation and Rab5a, influencing responsiveness to selexipag. CTRP7 emerged as a compelling biomarker for predicting responsiveness to prostacyclin analogs, potentially advancing the development of innovative PAH treatment strategies. Novel and SignificanceO_ST_ABSWhat Is Known?C_ST_ABSO_LIPulmonary arterial hypertension (PAH) is a life-threatening vascular disease with limited treatment options. C_LIO_LIAlthough pulmonary vasodilators have shown promise in managing PAH, the overall improvement in prognosis is modest. C_LIO_LIFurther research is needed to understand the molecular features of pulmonary vasodilators and identify biomarkers for appropriate selection. C_LI What New Information Does This Article Contribute?O_LIC1q/TNF-related protein 7 (CTRP7) was found to be elevated in the pulmonary artery smooth muscle cells (PASMCs) and plasma of patients with pulmonary arterial hypertension (PAH). C_LIO_LIThis study established a connection between inflammation and pulmonary vascular responsiveness via CTRP7-mediated internalization and degradation of the prostacyclin analog receptor. C_LIO_LIThis study indicated the possibility of using plasma CTRP levels as a clinical biomarker to monitor pulmonary responsiveness, which can contribute to the development of novel treatment strategies for patients with PAH. C_LI Pulmonary arterial hypertension (PAH) is a life-threatening and enigmatic lung vascular disorder characterized by progressive pulmonary vascular remodeling and vasoconstriction. Despite significant advancements in the treatment of PAH using pulmonary vasodilators, some individuals display limited responses, primarily due to a lack of understanding of the molecular features of each pulmonary vasodilator and the absence of a biomarker for appropriate selection. The present study aimed to identify promising biomarkers for predicting a patients responsiveness to pulmonary vasodilators through a two-step approach, involving RNA sequencing of PASMCs and the measurement of plasma levels. CTRP7 emerged as a prominent biomarker, displaying increased expression in both PASMCs and plasma obtained from patients with PAH. Mechanistically, IL-6 transcriptionally modulated CTPR7, leading to the internalization and degradation of PTGIR, resulting in a reduced response to selexipag (prostacyclin analog) in PASMCs. Integrating the human studies, a hypoxic mouse model exhibited lower PTGIR expression in pulmonary arteries, correlating with limited responses to selexipag treatment, which were ameliorated by silencing CTRP7 expression in pulmonary arteries using adeno-associated virus 6 transduction. This study collectively demonstrates that CTRP7 emerges as a compelling biomarker for predicting responsiveness to prostacyclin analogs, with the potential to advance the development of innovative PAH treatment strategies.

molecular biology↗

bioRxiv2021

Microstructural Properties of Human Brain Revealed by Fractional Anisotropy can Predict the After-effect of Intermittent Theta Burst Stimulation

Intermittent theta burst stimulation (iTBS) delivered by transcranial magnetic stimulation (TMS) produces a long term potentiation (LTP)-like after-effect useful for investigations of cortical function and of potential therapeutic value. However, the iTBS-evoked after-effect over the primary motor cortex (M1) as measured by changes in motor evoked potential (MEP) amplitude exhibits a largely unexplained variability across individuals. Here, we present evidence that individual differences in white and grey matter microstructural properties revealed by fractional anisotropy (FA) predict the magnitude of the iTBS-induced after-effect over M1. The MEP amplitude change in the early phase (5-10 min) post-iTBS was associated with FA values in white matter tracts such as right superior longitudinal fasciculus and corpus callosum. In contrast, the MEP amplitude change in the late phase (15-30 min) post-iTBS was associated with FA in grey matter, primarily in right frontal cortex. These results suggest that the microstructural properties of regions connected directly or indirectly to the target region (M1) are crucial determinants of the iTBS after-effect. FA values indicative of these microstructural differences can predict the potential effectiveness of rTMS for both investigational use and clinical application.

neuroscience↗

bioRxiv2020

Macromolecular tissue volume mapping of lateral geniculate nucleus subdivisions in living human brains

The human lateral geniculate nucleus (LGN) is composed mainly of the magnocellular and parvocellular subdivisions. The non-invasive identification of these subdivisions is, however, difficult due to the small size of the LGN. Here we propose a method to identify these subdivisions by combining two structural MR measures: high-resolution proton-density weighted images and macromolecular tissue volume maps. We collected MRI data from 15 healthy subjects and found that the spatial organization of these subdivisions identified by our method was consistent with post-mortem histological data. Furthermore, the stimulus selectivity in these regions measured by functional MRI was consistent with physiological studies. These results suggest that macromolecular tissue volume mapping is a promising approach to evaluating the tissue properties of LGN subdivisions in living humans. This method potentially will enable neuroscientific and clinical hypotheses about the human LGN to be tested.

neuroscience↗

bioRxiv2020

Physiological significance of proteolytic processing of Reelin revealed by cleavage-resistant Reelin knock-in mice

Reelin is a secreted protein that plays versatile roles in neuronal development and function, and hypoactivity of Reelin is implicated in many neuropsychiatric disorders. The strength of Reelin signaling is regulated by proteolytic processing, but its importance in vivo is not yet fully understood. Here, we generated Reelin knock-in (PA-DV KI) mice in which the key cleavage site of Reelin was abolished by mutation. As expected, the cleavage of Reelin was severely abrogated in the cerebral cortex and hippocampus of PA-DV KI mice. The amount of Dab1, whose degradation is induced by Reelin signaling, decreased in these tissues, indicating that the signaling strength of Reelin was augmented. The brains of PA-DV KI mice were largely structurally normal, but unexpectedly, the hippocampal layer was disturbed. This phenotype was ameliorated in hemizygote PA-DV KI mice, indicating that excess Reelin signaling is detrimental to hippocampal layer formation. The neuronal dendrites of PA-DV KI mice had more branches and were elongated compared to wild-type mice. These results present the first direct evidence of the physiological importance of Reelin cleavage and suggest that inhibition of Reelin cleavage would counteract neuropsychiatric disorders without causing severe systemic side effects.

neuroscience↗

bioRxiv2018

Microstructural properties of the vertical occipital fasciculus explain the variability in human stereoacuity

Stereopsis is a fundamental visual function that has been studied extensively. However, it is not clear why depth discrimination (stereoacuity) varies more significantly among people than other modalities. Previous studies reported the involvement of both dorsal and ventral visual areas in stereopsis, implying that not only neural computations in cortical areas but also the anatomical properties of white matter tracts connecting those areas can impact stereopsis and stereoacuity. Here, we studied how human stereoacuity relates to white matter properties by combining psychophysics, diffusion MRI (dMRI), and quantitative MRI (qMRI). We performed a psychophysical experiment to measure stereoacuity, and in the same participants we analyzed the microstructural properties of visual white matter tracts based on two independent measurements, dMRI (fractional anisotropy, FA) and qMRI (macromolecular tissue volume; MTV). Microstructural properties along the right vertical occipital fasciculus (VOF), a major tract connecting dorsal and ventral visual areas, were highly correlated with measures of stereoacuity. This result was consistent for both FA and MTV, suggesting that the structural-behavioral relationship reflects differences in neural tissue density, rather than differences in the morphological configuration of fibers. fMRI confirmed that binocular disparity stimuli activated the dorsal and ventral visual regions near VOF endpoints. No other occipital tracts explained the variance in stereoacuity. In addition, the VOF properties were not associated with differences in performance on a different psychophysical task (contrast detection). These series of experiments suggest that stereoscopic depth discrimination performance is, at least in part, constrained by dorso-ventral communication through the VOF.

neuroscience↗