Biology subjects

Kawata, K.

Publications and source records attributed to Kawata, K..

5 recordsLinked to original sources

bioRxiv2026

STING restrains calcium-dependent microglial phagocytosis and protects against neuronal loss and cognitive impairment during epileptogenesis

Epileptogenesis is accompanied by robust neuroinflammation, yet the molecular pathways linking innate immune activation to neuronal dysfunction remain incompletely defined. Given the established pro-inflammatory role of the stimulator of interferon genes (STING), we initially hypothesized that its loss would attenuate neuroinflammatory responses during epileptogenesis. Contrary to our expectation, we found that STING deficiency instead amplified microglial activation. Using a kainic acid mouse model of temporal lobe epilepsy (TLE), we show that STING-deficient microglia exhibit pronounced lysosomal expansion and enhanced phagocytic engulfment of neurons, leading to increased hippocampal neuronal loss and cognitive impairment. Mechanistically, STING deficiency increased the expression and altered the subcellular distribution of stromal interaction molecule 1 (STIM1), an endoplasmic reticulum Ca{superscript 2} sensor that mediates store-operated calcium entry (SOCE), resulting in dysregulated intracellular calcium dynamics and elevated SOCE activity. Pharmacological inhibition of SOCE reduced microglia-neuron interactions and microglial phagocytic engulfment, improved neuronal survival in the CA3 region of the hippocampus, and rescued cognitive deficits following status epilepticus. Collectively, these findings redefine STING as a negative regulator of microglial activation and identify a previously unrecognized STING-STIM1-SOCE axis that constrains calcium-dependent microglial phagocytosis during epileptogenesis, highlighting microglial calcium signaling as a potential therapeutic target in TLE.

neuroscience↗

bioRxiv2020

Metabolic labeling of RNA using multiple ribonucleoside analogs enables simultaneous evaluation of transcription and degradation rates

Gene expression is one of the factors determining cellular conditions, and its level is determined by the balance between transcription and RNA degradation. However, it has been not well elucidated how transcription and degradation are related to each other. To elucidate the relationship of them, methods enabling simultaneous measurement of transcription and degradation are required. Here, we report the development of "Dyrec-seq" to evaluate transcription and RNA degradation rates simultaneously, by using 4-thiouridine and 5-bromouridine. Using Dyrec-seq, we quantified the transcription and degradation rates of 4,702 genes in HeLa cells. Functional enrichment analysis showed that the transcription and degradation rates of genes are actually determined by the genes biological functions. Comparison of theoretical and experimental analysis results revealed that the amount of RNA was determined by the ratio of transcription to degradation rates, while the rapidity of responses to external stimuli was determined only by the degradation rate. This study emphasizes that degradation as well as transcription is important in determining the behavior of RNA.

systems biology↗

bioRxiv2020

Association between proteomic blood biomarkers and DTI/NODDI metrics in adolescent football players

The objective of the study was to examine the association between diffusion MRI techniques [diffusion tensor imaging (DTI) and neurite orientation/dispersion density imaging (NODDI)] and brain-injury blood biomarker levels [Tau, neurofilament-light (NfL), glial-fibrillary-acidic-protein (GFAP)] in high-school football and cross-country runners at their baseline, aiming to detect cumulative neuronal damage from prior seasons. Twenty-five football players and 8 cross-country runners underwent MRI and blood biomarker measures during preseason data collection. The whole-brain, tract-based spatial statistics was conducted for six diffusion metrics: fractional anisotropy (FA), mean diffusivity (MD), axial/radial diffusivity (AD, RD), neurite density index (NDI), and orientation dispersion index (ODI). Diffusion metrics and blood biomarker levels were compared between groups and associated within each group. The football group showed lower AD and MD than the cross-country group in various axonal tracts of the right hemisphere. Elevated ODI was observed in the football group in the right hemisphere of the corticospinal tract. Blood biomarker levels were consistent between groups except for elevated Tau levels in the cross-country group. Tau level was positively associated with MD and negatively associated with NDI in the corpus callosum of football players, but not in cross-country runners. Our data suggest that football players may develop axonal microstructural abnormality. Levels of MD and NDI in the corpus callosum were associated with serum Tau levels, highlighting the vulnerability of the corpus callosum against cumulative head impacts. Despite observing multimodal associations in some brain areas, neuroimaging and blood biomarkers may not strongly correlate to reflect the severity of brain damage.

neuroscience↗

bioRxiv2018

Association of physiological variables with football subconcussive head impacts: Why measure?

Subconcussive head impacts, defined as impacts to the cranium that do not result in clinical symptoms of concussion, are gaining traction as a major public health concern. Researchers begin to suggest subconcussive impact-dependent changes in various neurological measures. However, a contribution of physiological factors such as physical exertion and muscle damage has never been accounted. We conducted a prospective longitudinal study during a high school American football season to examine the association between physiological factors and subconcussive head impact kinematics. Fifteen high-school American football players volunteered in the study. A sensor-installed mouthguard recorded the number of head impacts, peak linear (PLA: g) and peak rotational (PRA: rad/s2) head accelerations from every practice and game. Serum samples were collected at 12 time points (pre-season baseline, five in-season pre-post games, and post-season) and assessed for the creatine kinase skeletal muscle-specific isoenzyme (CK-MM), as a surrogate for skeletal muscle damage. Physical exertion was estimated in the form of excess post-exercise oxygen consumption (EPOC) from heart rate data captured during five games via a wireless heart rate monitor. A total of 9,700 hits, 214,492 g, and 19,885,037 rad/s2 were recorded from 15 players across the study period. Mixed-effect regression models indicated that head impact kinematics (frequency, PLA, and PRA) were significantly and positively associated with CK-MM increase, but not with EPOC. There was a significant and positive association between CK-MM and EPOC. These data suggest that skeletal muscle damage effects should be considered when using outcome measures that may have an interaction with muscle damage, including inflammatory biomarkers and vestibular/balance tests.

physiology↗

bioRxiv2017

Trans-omic analysis reveals fed and fasting insulin signal across phosphoproteome, transcriptome, and metabolome

The concentration and temporal pattern of insulin selectively regulate multiple cellular functions. To understand how insulin dynamics are interpreted by cells, we constructed a trans-omic network of insulin action in FAO hepatoma cells from three networks--a phosphorylation-dependent cellular functions regulatory network using phosphoproteomic data, a transcriptional regulatory network using phosphoproteomic and transcriptomic data, and a metabolism regulatory network using phosphoproteomic and metabolomic data. With the trans-omic regulatory network, we identified selective regulatory networks that mediate differential responses to insulin. Akt and Erk, hub molecules of insulin signaling, encode information of a wide dynamic range of dose and time of insulin. Down-regulated genes and metabolites in glycolysis had high sensitivity to insulin (fasting insulin signal); up-regulated genes and dicarboxylic acids in the TCA cycle had low sensitivity (fed insulin signal). This integrated analysis enables molecular insight into how cells interpret physiologically fed and fasting insulin signals.\n\nHighlightsO_LIWe constructed a trans-omic network of insulin action using multi-omic data.\nC_LIO_LIThe trans-omic network integrates phosphorylation, transcription, and metabolism.\nC_LIO_LIWe classified signaling, transcriptome, and metabolome by sensitivity to insulin.\nC_LIO_LIWe identified fed and fasting insulin signal flow across the trans-omic network.\nC_LI

systems biology↗