Biology subjects

Andres, E.

Publications and source records attributed to Andres, E..

5 recordsLinked to original sources

bioRxiv2025

A ventral striatal learning signal reflecting individual differences in the success of fear extinction

Individual differences in fear extinction learning are centrally involved in anxiety vulnerability. We here investigate individual extinction differences using a model-free, data-driven approach, by applying Latent Class Growth Modeling (LCGM) to four in-house data sets from altogether N=234 healthy male participants. This revealed two distinct trajectory classes: fast extinguishers and slow extinguishers. This pattern was replicated in two independent public data sets (total N=275, female and male). In a subset of the in-house samples with functional magnetic resonance imaging (fMRI) data (n=122 males), we investigated the neural correlates of class membership, focusing on the ventral striatum (VS), a key area previously implicated in encoding extinction prediction errors (EPE). We found that fast extinguishers exhibited VS activity at the time of unconditioned stimulus omission early in extinction, consistent with an EPE signal, whereas this signal only appeared late in extinction in slow extinguishers. These findings suggest that extinction success is shaped by how the VS learns safety.

neuroscience↗

bioRxiv2025

Spine-brain dynamics during human defensive threat-reactions

Synchrony between central and autonomic nervous system responses during threat rely on spine-brain interactions. Activation of the parasympathetic autonomic nervous system during acute threat has been linked to optimized action preparation and longer-term stress-resilience. However, it is unclear how this is orchestrated by spine-brain interactions during our widely used models of threat conditioning. Here we used a well-established threat conditioning procedure to test whether freezing-related bradycardia modulates the strength of motor- and sensory-relevant spinal-brain connectivity patterns. Conditioning elicited the expected autonomic and psychophysiological responses, with significant bradycardia and heightened differentiation between conditioned stimuli. Heart rate bradycardia modulated activity in the cingulate cortex and spinal cord, emphasizing their role in freezing. Notably, bradycardia-modulated spinal cord activity during threat was functionally coupled with motor cortex activity, suggesting a preparatory response for defensive actions. Establishing these effects for the first time in humans helps discovery of biomarkers for threat coping-relevant body-brain interactions, essential for clinical evaluations.

neuroscience↗

bioRxiv2025

The central clock drives metabolic rhythms in muscle stem cells

Circadian rhythms are essential for organismal health. Satellite cells (SCs), the muscle resident stem cells, maintain a state of quiescence yet exhibit robust circadian oscillations at the transcriptional level. Although peripheral clocks have been extensively studied in various tissues, how the intrinsic clock of stem cells interacts with the central, distal clock is largely unknown. We used SC-specific reconstitution of the essential clock gene Bmal1 to elucidate the role of the local SC clock and its interplay with the central clock in the mouse brain and found that daily transcriptional control of metabolic processes in SCs depend on central clock input, independent of the SC clock. Central clock-driven genes were involved in lipid metabolism, functionally important for SC-mediated muscle repair, and autophagy was required for their oscillation. In summary, we provide the first evidence of circadian coordination of central and local clocks for control of rhythmic gene expression in quiescent stem cells. HighlightsO_LIBrain:satellite cell clock communication restores rhythms of core clock machinery in quiescent satellite cells C_LIO_LIBrain inputs are the dominant regulator of transcript rhythms in SCs, driving the oscillation of lipid metabolic genes. C_LIO_LIAutophagy in satellite cells is required for the oscillation of lipid metabolic genes. C_LIO_LIEarly phases of muscle regeneration depend on brain-driven circadian signals. C_LI

cell biology↗

bioRxiv2025

Orally Delivered Milk-Derived Nanovesicles Loaded with Connexin 43 Peptides forTargeted Cardiac Ischemia-Reperfusion Therapy

Extracellular vesicles have emerged as promising nanocarriers for targeted drug delivery, but their therapeutic potential is limited by challenges related to administration route, loading, targeted delivery and production at scale. Here, we report an innovative approach for targeted delivery of therapeutic peptides to injured tissues using milk-derived small extracellular vesicles (mEVs) as an abundant, safe, orally administrable nanoplatform. We demonstrate that a sub-population of mEVs naturally contain Connexin 43 (Cx43) and its Carboxyl-Terminal (CT) polypeptides, which have been shown to play crucial roles in wound healing and tissue repair. Leveraging this intrinsic property, we developed an esterification method to efficiently and uniformly load mEVs with enhanced levels of an exogenous Cx43 CT peptide (CT11 - RPRPDDLEI), as assessed by flow cytometry-based vesicle quantification and mass spectrometry. These engineered mEVs exhibited remarkable injury targeting capabilities, with > 30-fold increases in uptake by injured cells compared to non-wounded cells in vitro and preferential accumulation in wounded tissues in vivo. Notably, CT11-loaded mEVs orally administered after myocardial infarction reduced infarct size by >60% and preserved heart function in a mouse model of ischemia-reperfusion injury. This study represents a significant advance in nanomedicine, demonstrating the utilization of naturally occurring milk-derived extracellular vesicles as an oral delivery system for therapeutic peptides, achieving unprecedented targeting efficiency and efficacy in the treatment of myocardial ischemia-reperfusion injury.

bioengineering↗

bioRxiv2022

Arousal defines the conditions for facilitation by L-DOPA of extinction consolidation and associated prefrontal activity

Even after successful extinction, conditioned fear can return. Strengthening the consolidation of the fear-inhibitory safety memory formed during extinction is one way to counteract return of fear. In this preregistered direct replication study in male participants, we confirm that spontaneous post-extinction reactivations of a neural activation pattern evoked in the ventromedial prefrontal cortex (vmPFC) during extinction predict extinction memory retrieval 24 h later. We do not confirm that L-DOPA administration after extinction enhances retrieval and that this is mediated by enhancement of the number of vmPFC reactivations. However, additional non-preregistered analyses reveal a beneficial effect of L-DOPA on extinction retrieval when controlling for the trait-like stable baseline levels of salivary alpha-amylase enzymatic activity (trait sAA) levels that participants show on the three experimental days. Further, trait sAA negatively predicts retrieval, and this effect is rescued by L-DOPA treatment. Our results suggest that individuals with high basal levels of sympathetic nervous system (SNS) activity may have poor extinction and that L-DOPA may be selectively beneficial for these individuals, which holds potential for clinical applications.

neuroscience↗