Biology subjects

Strauss, B.

Publications and source records attributed to Strauss, B..

7 recordsLinked to original sources

bioRxiv2026

Automated pup-level analysis reveals distinct effects of prenatal CBD and THC exposure on maternal retrieval

This study examined how prenatal CBD and {Delta}9-tetrahydrocannabinol (THC) exposure affects maternal caregiving in C57BL/6J mice. We developed the Machine-Automated Scoring of the Pup Retrieval Test (MAS-PRT) to overcome limitations of manual behavioral scoring. MAS-PRT integrates Multi-Animal DeepLabCut for dam and pup tracking with Detectron2 for dynamic nest reconstruction. Validated against 170 manually annotated retrieval trials, the pipeline showed high concordance with manual measurements and enabled reproducible extraction of encounter latency, retrieval latency, and locomotor trajectories. Prenatal exposure did not impair general nest-building or overall home-cage maternal care. However, pups from both CBD and THC groups showed reduced body weight at postnatal day 5. Cox proportional hazards modeling revealed divergent effects by compound: CBD-exposed dams exhibited a weight-dependent increase in probability of encountering and retrieving lighter pups, independent of pup sex. Spatial tracking further showed that dams traversed significantly shorter total trajectories when retrieving female progeny exposed to either compound. Longitudinal trial-by-trial analysis indicated intact task acquisition in controls and CBD dams, whereas THC dams displayed a flattened learning curve driven by lower retrieval latencies on initial trials. Together, these findings indicate that prenatal cannabinoid exposure does not produce generalized disruption of maternal care but instead induces compound-specific alterations in maternal reactivity, retrieval kinematics, and learning dynamics.

animal behavior and cognition↗

bioRxiv2024

Cardiomyocyte STIM1 downregulation exacerbates post-Myocardial Infarction remodeling by dysregulating mitochondrial ultrastructure and metabolic signaling

BackgroundStromal interaction molecule 1 (STIM1) is a key regulator of intracellular calcium (Ca{superscript 2}) homeostasis and mitochondrial function, two tightly coupled processes that critically determine electro-mechanical function and post-myocardial infarction (MI) remodeling. HypothesisWe hypothesized that cardiomyocyte STIM1 deficiency induced by AAV9-mediated knockdown triggers mitochondrial and metabolic remodeling that alters the electrophysiological (EP) substrate and exacerbates post-MI heart failure. MethodsEight-week-old mice received cardiotropic AAV9-mediated delivery of short hairpin RNA targeting STIM1 (AAV9-shSTIM1) or a control construct (AAV9-shLuc/PBS). Four weeks later, in vivo echocardiography followed by ex vivo optical action potential (AP) mapping were performed to determine the impact of myocardial STIM1 downregulation on mechanical and EP properties. Electron microscopy and western blotting were performed to assess mitochondrial network architecture, dynamics and related metabolic signaling. A separate cohort of mice underwent a 30-minute coronary occlusion followed by reperfusion to induce MI. One week post-MI, left ventricular (LV) function, structural remodeling, and EP properties were assessed in mice with and without myocardial STIM1 knockdown. ResultsAAV9-shSTIM1 delivery markedly reduced cardiomyocyte STIM1 expression. STIM1 downregulation induced extensive mitochondrial fragmentation, increased DRP1 phosphorylation at S616 (+55%, p=0.0057), reduced OPA1 expression, and altered AMPK-dependent signaling (reduced phospho-ACC and phospho-Raptor). These mitochondrial and metabolic abnormalities were accompanied by EP instability. In response to in vivo I/R injury, shSTIM1 mice exhibited significantly greater LV dysfunction (-44.3% vs. -12.2% fractional shortening, p<0.0001) and more pronounced structural and EP remodeling with formation of spatially discordant AP alternans 1-week following MI indicative of accelerated heart failure progression. ConclusionsAAV9-mediated STIM1 knockdown exacerbates post-MI cardiac dysfunction likely through impaired mitochondrial dynamics and disrupted metabolic signaling. Beyond worsening post-MI function, STIM1 deficiency alone induces profound EP remodeling, underscoring the pivotal role of cardiomyocyte STIM1 in coordinating mitochondrial homeostasis, electrical stability, and cardiac recovery after injury.

physiology↗

bioRxiv2023

Sexual differences in neuronal and synaptic properties across subregions of the mouse insular cortex

BackgroundThe insular cortex (IC) plays a pivotal role in processing interoceptive and emotional information, offering insights into sex differences in behavior and cognition. The IC comprises two distinct subregions: the anterior insular cortex (aIC), that processes emotional and social signals, and the posterior insular cortex (pIC), specialized in interoception and perception of pain. Pyramidal projection neurons within the IC integrate multimodal sensory inputs, influencing behavior and cognition. Despite previous research focusing on neuronal connectivity and transcriptomics, there has been a gap in understanding pyramidal neurons characteristics across subregions and between sexes. MethodsAdult male and female C57Bl/6J mice were sacrificed and tissue containing the IC was collected for ex vivo slice electrophysiology recordings that examined baseline sex differences in synaptic plasticity and transmission within aIC and pIC subregions. ResultsClear differences emerged between aIC and pIC neurons in both males and females: aIC neurons exhibited distinctive features such as larger size, increased hyperpolarization, and a higher rheobase compared to their pIC counterparts. Furthermore, we observed variations in neuronal excitability linked to sex, with male pIC neurons displaying a greater level of excitability than their female counterparts. We also identified region-specific differences in excitatory and inhibitory synaptic activity and the balance between excitation and inhibition in both male and female mice. Adult females demonstrated greater synaptic strength and maximum response in the aIC compared to the pIC. Lastly, synaptic long-term potentiation occurred in both subregions in males but was specific to the aIC in females. ConclusionsWe conclude that there are sex differences in synaptic plasticity and excitatory transmission in IC subregions, and that distinct properties of IC pyramidal neurons between sexes could contribute to differences in behavior and cognition between males and females. Highlights- Distinctions specific to sex are present within subregions of the insular cortex (IC) in C57Bl/6J mice. - Pyramidal neurons in the anterior IC (aIC) exhibited larger size and distinct electrical properties. Adult females exhibited stronger synaptic responses in the aIC. - Conversely, male posterior insular cortex neurons displayed increased excitability. - Synaptic long-term potentiation was observed in both subregions in males, but it was exclusive to the aIC in females. - Sex-based variations in various aspects of excitatory transmission within IC subregions could contribute to differences in behavior and cognition between males and females. Plain language summaryThis study investigates differences in the insular cortex (IC), a region of the brain responsible for emotions and sensory perceptions, between male and female mice. The IC has two parts: the front (aIC) deals with emotions and social cues, while the back (pIC) is focused on sensing pain and bodily sensations. We examined specific brain cells called pyramidal neurons in both aIC and pIC and discovered noteworthy distinctions between these neurons in adult male and female mice. Firstly, aIC neurons were larger and had unique electrical properties in both male and female mice. Males had more excitable pIC neurons compared to females, indicating that their neurons were more likely to transmit signals. We also explored how these neurons communicate with each other through connections known as synapses. In adult females, the aIC had stronger connections than the pIC. Finally, we observed that specific types of basic synaptic learning occurred exclusively in males in the aIC. These findings underscore significant disparities in the IC between males and females, offering valuable insights into the potential reasons behind variations in behaviors and emotions between sexes.

neuroscience↗

bioRxiv2023

Adaptive Group Behavior of Fragile X Mice in Unfamiliar Environments

Fragile X Syndrome (FXS) stands out as a prominent cause of inherited intellectual disability and a prevalent disorder closely linked to autism. FXS is characterized by substantial alterations in social behavior, encompassing social withdrawal, avoidance of eye contact, heightened social anxiety, increased arousal levels, language deficits, and challenges in regulating emotions. Conventional behavioral assessments primarily focus on short-term interactions within controlled settings. In this study, we conducted a comprehensive examination of the adaptive group behavior of FXS mice over a three-day period, without introducing experimental interventions or task-based evaluations. The data unveiled intricate behavioral anomalies, with the most significant changes manifesting during the initial adaptation to unfamiliar environments. Notably, certain behaviors exhibited a gradual return to typical patterns over time. This dynamic FXS phenotype exhibited heightened activity, featuring increased exploration, amplified social interest, and an unconventional approach to social interactions characterized by a higher frequency of shorter engagements. These findings contribute to the growing understanding of social behavior in individuals with FXS and underscore the significance of comprehending their adaptive responses in various environmental contexts.

animal behavior and cognition↗

bioRxiv2020

Bioassemblying Macro-Scale, Lumnized Airway Tubes of Defined Shape via Multi-Organoid Patterning and Fusion

Epithelial, stem-cell derived organoids are ideal building blocks for tissue engineering, however, scalable and shape-controlled bioassembly of epithelial organoids into larger and anatomical structures has yet to be achieved. Here, a robust organoid engineering approach, Multi-Organoid Patterning and Fusion (MOrPF), is presented to assemble individual airway organoids of different sizes into upscaled, scaffold-free airway tubes with pre-defined shapes. Multi-Organoid Aggregates (MOAs) undergo accelerated fusion in a matrix-depleted, free-floating environment, possess a continuous lumen and maintain prescribed shapes without an exogenous scaffold interface. MOAs in the floating culture exhibit a well-defined three-stage process of inter-organoid surface integration, luminal material clearance and lumina connection. The observed shape stability of patterned MOAs is confirmed by theoretical modelling based on organoid morphology and the physical forces involved in organoid fusion. Immunofluorescent characterization shows that fused MOA tubes possess an unstratified epithelium consisting mainly of tracheal basal stem cells. By generating large, shape-controllable organ tubes, MOrPF enables upscaled organoid engineering towards integrated organoid-devices and structurally complex organ tubes.

bioengineering↗

bioRxiv2020

The proportion of periportal mesenchyme to ductal epithelial cells acts as a proliferative rheostat in liver regeneration

In the homeostatic liver, ductal cells intermingle with a microenvironment of endothelial and mesenchymal cells to form the functional unit of the portal tract. Ductal cells proliferate rarely in homeostasis but do so transiently after tissue injury to replenish any lost epithelium. We have shown that liver ductal cells can be expanded as liver organoids that recapitulate several of the cell-autonomous mechanisms of regeneration, but lack the stromal cell milieu of the biliary tract in vivo. Here, we describe a subpopulation of SCA1+ periportal mesenchymal cells that closely surrounds ductal cells in vivo and exerts a dual control on their proliferative capacity. Mesenchymal-secreted mitogens support liver organoid formation and expansion from differentiated ductal cells. However, direct mesenchymal-to-ductal cell-cell contact, established following a microfluidic co-encapsulation that enables the cells to self-organize into chimeric organoid structures, abolishes ductal cell proliferation in a mesenchyme-dose dependent manner. We found that it is the ratio between mesenchymal and epithelial cell contacts that determines the net outcome of ductal cell proliferation both in vitro, and in vivo, during damage-regeneration. SCA1+ mesenchymal cells control ductal cell proliferation dynamics by a mechanism involving, at least in part, Notch signalling activation. Our findings underscore how the relative abundance of cell-cell contacts between the epithelium and its mesenchymal microenvironment are key regulatory cues involved in the control of tissue regeneration. SummaryIn the homeostatic liver, the ductal epithelium intermingles with a microenvironment of stromal cells to form the functional unit of the portal tract. Ductal cells proliferate rarely in homeostasis but do so transiently after tissue injury. We have shown that these cells can be expanded as liver organoids that recapitulate several of the cell-autonomous mechanisms of regeneration, but lack the stromal cell milieu of the portal tract in vivo. Here, we describe a subpopulation of SCA1+ periportal mesenchymal niche cells that closely surrounds ductal cells in vivo and exerts a dual control on their proliferative capacity. Mesenchymal-secreted mitogens support liver organoid formation and expansion from differentiated ductal cells. However, direct mesenchymal-to-ductal cell-cell contact, established through a microfluidic co-encapsulation method that enables the cells to self-organize into chimeric organoid structures, abolishes ductal cell proliferation in a mesenchyme-dose dependent manner. We found that it is the ratio between mesenchymal and epithelial cell contacts that determines the net outcome of ductal cell proliferation both in vitro, and in vivo, during damage-regeneration. SCA1+ mesenchymal cells control ductal cell proliferation dynamics by a mechanism involving, at least in part, Notch signalling activation. Our findings re-evaluate the concept of the cellular niche, whereby the proportions of cell-cell contacts between the epithelium and its mesenchymal niche, and not the absolute cell numbers, are the key regulatory cues involved in the control of tissue regeneration.

developmental biology↗

bioRxiv2019

Renewal theory provides a universal quantitative framework to characterise the continuous regeneration of rotational events in cardiac fibrillation

BackgroundCardiac fibrillation is thought to be maintained by rotational activity, with pivoting regions called phase singularities (PSs). Despite a century of research, no clear quantitative framework exists to model the fundamental processes responsible for the continuous formation and destruction of rotors in fibrillation.\n\nObjectiveWe conducted a multi-modality, multi-species study of AF/VF under the hypothesis that PS formation/destruction in fibrillation can be modelled as self-regenerating renewal processes, producing exponential distributions of inter-event times governed by constant rate-parameters defined by the prevailing properties of the system.\n\nMethodsPS formation/destruction was studied and cross-validated in 5 models, using basket recordings and optical mapping from: i) human persistent AF (n = 20), ii) tachypaced sheep AF (n = 5), iii) rat AF (n = 4), iv) rat VF (n = 11) and v) computer simulated AF (SIM). Hilbert phase maps were constructed. PS lifetime data were fitted by exponential probability distribution functions (PDFs) computed using maximum entropy theory, and the rate parameter ({lambda}) determined. A systematic review was conducted to cross-validate with source data from literature.\n\nResultsPS destruction/formation distributions showed good fits to an exponential in all systems (R2 [≥] 0.90). In humans,{lambda} = 4.6%/ms (95%CI,4.3,4.9)), sheep 4.4%/ms (95%CI,4.1,4.7)), rat AF 38%/ms (95%CI,22,55), rat VF 46%/ms (95%CI,31.2,60.2) and SIM 5.4%/ms (95%CI,4.1,6.7). All PS distributions identified through systematic review were exponential with {lambda} comparable to experimental data.\n\nConclusionThese results provide a universal quantitative framework to explain rotor formation and destruction in AF/VF, and a platform for therapeutic advances in cardiac fibrillation.

physiology↗