Biology subjects

Nishitani, S.

Publications and source records attributed to Nishitani, S..

5 recordsLinked to original sources

bioRxiv2025

Linking Pain and Delirium via Microglial Activation: A Mouse Study Using BSEEG, Behavioral Assays, Immunohistochemistry, and RNA Sequencing

BackgroundThe rising incidence of delirium in surgical and critical care settings, especially in older patients, calls for improved preventative and management strategies. Chronic pain is increasingly recognized as a key risk factor for delirium, and microglial activation may be the central mediator linking these two conditions. MethodsWe used a spared nerve injury (SNI) model of persistent neuropathic pain in tandem with a postoperative delirium (POD) mouse model. Pain assessments, electroencephalography (EEG) recording, and immunofluorescence were performed to characterize pain and delirium-like states. Microglia were isolated for RNA-seq to elucidate gene expression changes comprehensively. ResultsSNI mice showed persistent mechanical hypersensitivity from Day 7 onwards and demonstrated disrupted sleep-wake patterns in EEG indices. Immunofluorescence revealed sustained microglial activation in both the hippocampus and cortex following SNI. RNA-seq analyses indicated the upregulation of pro-inflammatory pathways (e.g., interleukin-6 production, NF-{kappa}B signaling) in SNI mice that also underwent head-mount surgery. Notably, the coincidence of persistent pain and an acute delirium-like state further exacerbated neuroinflammation. ConclusionOur findings suggest that neuropathic pain-induced microglial activation primes the brain for exaggerated inflammatory responses under additional surgical stress, potentially worsening delirium. Further investigations into microglia-focused therapies may inform novel strategies for mitigating delirium in patients with neuropathic pain.

neuroscience↗

bioRxiv2025

Non-linear Age-related Change in Human Interleukin-11 and the receptor subunit alpha DNA Methylation

IntroductionInterleukin-11 (IL-11) is a cytokine involved in inflammatory processes and a previous study showed that blocking or knocking down IL11 in mice prolongs a healthy lifespan. This study investigates DNA methylation (DNAm) changes in the IL11 and IL-11 receptor subunit alpha (IL-11RA) gene across ages to reveal how aging might influence IL-11 production and sensitivity. MethodsA genome-wide DNAm database focusing on Cytosine-phosphate-Guanine (CpG) sites within the IL11 and IL11RA was analyzed. Hierarchical regression analyses examined the relationship between DNAm, age, and the squared age term for quadratic associations. ResultsThe database comprised 10,297 samples (5,156 males and 5,141 females) with a mean age of 53.9 years (SD = 14.1 years). The majority of IL11 and IL11RA CpG sites in the TSS1500 and 3UTR regions exhibited significant inverse U-shaped associations with age. DNAm levels were low during youth, increased in middle age (40s-50s), and decreased again in older age. ConclusionThe observed inverse U-shaped DNAm patterns in the IL11 and IL11RA suggest n non-linear, age-related regulation of IL-11 expression and sensitivity. These findings indicate that IL-11 may have different roles across life stages and suggest that therapeutic interventions targeting IL-11 should consider age-specific effects.

genetics↗

bioRxiv2025

Glial Contribution to the Pathogenesis of Post-Operative Delirium Revealed by Multi-omic Analysis of Brain Tissue from Neurosurgery Patients

Post-operative delirium (POD) is a common complication after surgery especially in elderly patients, characterized by acute disturbances in consciousness and cognition, which negatively impacts long-term outcomes. Effective treatments remain elusive due to the unclear pathophysiology of POD. To address the knowledge gap, we investigated DNA methylation profiles and gene expression changes in brain cells from POD and non-POD patients who underwent brain resection surgery for medication refractory epilepsy. DNA methylation analysis revealed alteration in epigenetic status of immune and inflammation-related genes. Single-nucleus RNA sequencing (snRNAseq) identified POD-specific glial cell alterations, particularly in microglia, where neuroinflammation was strongly enhanced, consistent with epigenetic findings. Astrocytes exhibited changes in synapse-related functions and migration. Furthermore, downstream analysis indicated similarities between POD-associated glial cell states and pathologies such as encephalitis and dementia. Overall, this study--the first multi-omics analysis of brain tissue from POD patients--provides direct evidence of glial cell contributions to POD pathogenesis, and highlights potential therapeutic targets.

neuroscience↗

bioRxiv2024

Association Between Relational Mobility and DNA Methylation in Oxytocin Receptor Gene: A Social Epigenetic Study

DNA methylation is a type of epigenetic modification known to exhibit fluctuations in response to environmental factors. The association of macrosocial factors, such as interpersonal mobility, on methylation has seldom been investigated. This study aimed to examine the association of relational mobility, defined as the extent to which individuals can form and replace social relationships, on the DNA methylation of oxytocin receptor genes. DNA was extracted from the buccal cells of 95 adult participants (50 men and 45 women) and subjected to microarray analysis of DNA methylation using Illumina EPIC v2.0. The findings indicate that the oxytocin receptor genes methylation level was higher in individuals residing in low relational mobility social environments. The CpG site associated with relational mobility is an enhancer region, indicating that social environments with low relational mobility exert a suppressive effect on the transcriptional efficiency of the oxytocin receptor gene. Significance StatementThe association between DNA methylation of the oxytocin receptor gene and relational mobility was examined in 95 adults in their 20s to 60s, and found that those living in social environments with lower levels of relationship mobility had higher rates of DNA methylation of the oxytocin receptor gene. This study is a novel approach to a problem discussed in the social sciences using new analytical techniques in epigenomics.

genetics↗

bioRxiv2023

Covalent Attachment of Horseradish Peroxidase to Single-Walled Carbon Nanotubes for Hydrogen Peroxide Detection

Single-walled carbon nanotubes (SWCNTs) are desirable nanoparticles for sensing biological analytes due to their photostability and intrinsic near-infrared fluorescence. Previous strategies for generating SWCNT nanosensors have leveraged nonspecific adsorption of sensing modalities to the hydrophobic SWCNT surface that often require engineering new molecular recognition elements. An attractive alternate strategy is to leverage pre-existing molecular recognition of proteins for analyte specificity, yet attaching proteins to SWCNT for nanosensor generation remains challenging. Towards this end, we introduce a generalizable platform to generate protein-SWCNT-based optical sensors and use this strategy to synthesize a hydrogen peroxide (H2O2) nanosensor by covalently attaching horseradish peroxidase (HRP) to the SWCNT surface. We demonstrate a concentration-dependent response to H2O2, confirm the nanosensor can image H2O2 in real-time, and assess the nanosensors selectivity for H2O2 against a panel of biologically relevant analytes. Taken together, these results demonstrate successful covalent attachment of enzymes to SWCNTs while preserving both intrinsic SWCNT fluorescence and enzyme function. We anticipate this platform can be adapted to covalently attach other proteins of interest including other enzymes for sensing or antibodies for targeted imaging and cargo delivery.

bioengineering↗