Biology subjects

Thai, T.

Publications and source records attributed to Thai, T..

5 recordsLinked to original sources

bioRxiv2026

Isoflurane anesthesia CNS recovery state: ultra-slow oscillations and cellular-stress-responsive gene expression

General anesthesia and NREM sleep share slow-wave EEG features, yet whether anesthesia substitutes for physiological sleep remains unclear. We compared recovery from 4h of isoflurane anesthesia (IA) with time-matched sleep and sleep deprivation (SD) in male C57BL/6J mice using continuous EEG/EMG recordings and frontal cortex RNA sequencing. IA recovery produced transient, rebound arousal, reduced early NREM and REM sleep, and, fragmented subsequent NREM bouts, and persistant, ultra-slow EEG-oscillations that normalized within two weeks. Whereas, SD induced consolidated rebound sleep and slow wave activity. Transcriptomic profiling at ZT6 showed that IA and SD induced largely distinct cortical gene-expression programs. IA preferentially enriched integrated stress response and unfolded protein response genes, whereas SD showed a comparatively orthogonal, growth-permissive, mTOR-associated profile. Although IA-induced gene-expression suggests cellular stress, corticosterone measurements argued against systemic stress as the primary driver. These findings indicate that isoflurane recovery is neurophysiologically and molecularly distinct from restorative sleep.

neuroscience↗

bioRxiv2025

Aging diminishes interlaminar functional connectivity in the mouse cortical V1 and CA1 hippocampal regions

Aging disrupts brain network integration and is a significant risk factor for cognitive decline and neurological diseases, yet the circuit-level mechanisms underlying these changes remain unclear. Most previous studies have utilized cross-sectional or acute approaches, limiting insights into the longitudinal dynamics of the neural network. In this study, we chronically recorded laminar electrophysiological activity in both the primary visual cortex (V1) and hippocampal CA1 region of young (2-month-old) and aged (13-month-old) mice over 16 weeks. This approach allowed us to directly assess how aging modulates functional connectivity within hierarchically connected cortical and hippocampal circuits. We found that single-unit spiking activity and the signal-to-noise ratio were largely preserved in aged versus young mice, suggesting intact neuronal firing properties. However, aged mice showed global reductions in local field potential (LFP) power and a selective decrease in coherence across delta, alpha-beta, and gamma frequency bands within and between cortical layers and V1-CA1 pathways, while phase amplitude coupling remained unaffected. Interestingly, population level excitatory activity in CA1 was increased in aged animals. These findings indicate that aging selectively impairs network-level synchrony and temporal coordination in specific frequency bands and regions, with minimal loss of single-neuron function. Our results highlight the necessity of longitudinal, multi-region measurements to uncover the multi-scale vulnerabilities of the aging brain. Understanding the depth- and region-dependent circuit changes will guide strategies to preserve cortical-hippocampal communication and cognitive function in aging, as well as enhance neural interface technologies for older populations. NEW & NOTEWORTHYAging non-uniformly degrades cortico-hippocampal networks, leading to region- and frequency-specific breakdowns in coordinated activity. While single-neuron activity remains preserved, disruptions in frequency-selective synchrony (delta and alpha-beta) were observed in aged mice, indicating impaired V1-CA1 communication as a marker of aging rather than neuronal degeneration. By separating single-neuron activity and large-scale dynamics, we reveal that aging alters communication between sensory and memory systems, underscoring the need for longitudinal approaches to capture age-related impairments in laminar connectivity.

neuroscience↗

bioRxiv2025

Hypermyelination Improves Strength and Detection of Neuronal Activity in the CA1 Hippocampus and Facilitates Neuroprotection in FusOLcKO Mice

1.0.Loss of oligodendrocytes (OLs) and myelin impairs cortical neuronal firing and network stability, whereas enhancement of oligodendrogenesis improves electrophysiological stability in cortex and, to a lesser extent, hippocampus. OLs exhibit regional heterogeneity, especially in their ability to synthesize cholesterol, a critical driver of myelin wrapping and ensheathment of axons. Conditional depletion of the Fused in sarcoma (Fus) gene in OLs, referred to as FusOLcKO, increases cholesterol biosynthesis, myelin thickness, and tissue cholesterol content. We examine whether this hypermyelination alters extracellular recordings across the layers of visual cortex and the underlying hippocampal CA1 over 16 weeks. In FusOLcKO mice, visually-evoked single-unit detectability and firing rate in CA1 increased relative to wild-type littermates, whereas cortical recordings showed no improvement. At the population level, FusOLcKO cortex exhibited reduced firing rates and lower functional connectivity, indicating altered network dynamics. Post-mortem histology revealed higher neuron density in recorded cortex and greater excitatory synapse density in CA1 of FusOLcKO mice suggesting region-specific neuroprotection and synaptic strengthening. These results demonstrate that cholesterol-driven hypermyelination enhances chronic hippocampal recordings while disrupting cortical network communication. Our study highlights myelins region-dependent roles in supporting single-cell reliability, tuning population dynamics, and maintaining circuit integrity under chronic perturbation. 2.0. SIGNIFICANCE STATEMENTMyelin critically regulates neural circuit function via conduction and metabolic support. Here, we show that cholesterol-driven hypermyelination in FusOLcKO mice augments single-unit detection and firing in hippocampal CA1 but reduces population firing and interlaminar connectivity within the cortex. These findings reveal a dual role for myelin: it can both safeguard specific circuit activity and perturb large-scale cortical communication. Understanding these dynamics is essential for designing myelin-targeted therapies in neurodegenerative disorders.

neuroscience↗

bioRxiv2025

Myofibroblasts reduce angiogenesis and vasculogenesis in a vascularized microphysiological model of lung fibrosis

Lung fibrosis, characterized by chronic and progressive scarring, has no cure. Hallmarks are the accumulation of myofibroblasts and extracellular matrix, as well as vascular remodeling. The crosstalk between myofibroblasts and vasculature is poorly understood, with conflicting reports on whether angiogenesis and vessel density are increased or decreased in lung fibrosis. We developed a microphysiological system that recapitulates the pathophysiology of lung fibrosis and disentangles myofibroblast-vascular interactions. Lung myofibroblasts maintained their phenotype in 3D without exogenous TGF-{beta} and displayed anti-angiogenic and anti-vasculogenic activities when cultured with endothelial cells in a microfluidic device. These effects, including decreased endothelial sprouting, altered vascular morphology, and increased vascular permeability, were mediated by increased TGF-{beta}1 and reduced VEGF secretion. Pharmacological interventions targeting these cytokines restored vascular morphology and permeability, demonstrating the potential of this model to screen anti-fibrotic drugs. This system provides insights into myofibroblast-vascular crosstalk in lung fibrosis and offers a platform for therapeutic development.

bioengineering↗

bioRxiv2022

The germline factor DDX4 contributes to the chemoresistance of small cell lung cancer cells

Human cancers often re-express germline factors, yet their mechanistic role in oncogenesis and cancer progression remains unknown. Here we demonstrate that DDX4, a germline factor and RNA helicase conserved in all multicellular organisms, contributes to epithelial mesenchyme transition (EMT)-like features and cisplatin resistance in small cell lung cancer (SCLC) cells. DDX4 depletion in H69AR and SHP77 cell lines decreased motility and resistance to cisplatin, whereas its overexpression increased these features. Proteomic analysis suggests that DDX4 upregulates metabolic protein expression related to DNA repair and immune/inflammatory response, suggesting its fundamental function may be in regulating cellular metabolism. Consistent with these trends in cell lines, DDX4 depletion compromised in vivo tumor development while its overexpression enhanced tumor growth even after cisplatin treatment in nude mice. Although the DDX4 expression level in somatic tumors is generally low compared to that in the germline, the relatively higher DDX4 expression in SCLC patients correlates with decreased survival and shows increased expression of EMT and cisplatin resistance markers. Taken together, we conclude that DDX4 influences the survival of SCLC patients by altering cellular metabolism in response to environmental cues such as drug treatments. This fundamental function of DDX4 as a germline factor might be applicable in other cancer types that express DDX4 and may serve as a key to combat specific tumors that are highly resistant to treatments. HighlightsO_LIDDX4 contributes to cellular motility and drug resistance in SCLC cells. C_LIO_LIDDX4-overexpression globally alters the proteome and suppresses cytokine production. C_LIO_LIDDX4 promotes tumorigenesis and drug resistance in vitro and in vivo. C_LIO_LIDDX4 expression correlates with survival in SCLC patients and with immune/inflammatory response both in cell lines and patient samples. C_LI

cancer biology↗