Biology subjects

Kuchar, M.

Publications and source records attributed to Kuchar, M..

7 recordsLinked to original sources

bioRxiv2024

Effects of serotonergic psychedelics on synaptogenesis and immediate early genes expression - comparison with ketamine, fluoxetine and lithium

BackgroundRecent evidence suggests that psychedelics are able to induce rapid and long-lasting antidepressant effects. The generally acknowledged explanation for these traits is the phenomenon of neuroplasticity, although exact underlying molecular mechanisms remain unclear. AimsThis study investigates selected neuroplastic effects of psilocin, lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT) in direct comparison with ketamine, fluoxetine and lithium after acute (1 h) and/or prolonged (24 h) treatment in vitro. MethodsRat primary cortical cultures were treated with 10 {micro}M psilocin, 1 {micro}M lysergic acid diethylamide (LSD), 90 {micro}M N, N-dimethyltryptamine (DMT), 1 {micro}M ketamine, 10 {micro}M fluoxetine and 5 mM lithium. Analysis of synaptic puncta was performed; puncta of presynaptic marker synapsin I/II, postsynaptic density protein 95 (PSD-95), and their co-localization (established synapse) were assessed 24 h after drug treatment. Next, expressions of immediate early genes (IEGs) encoding activity-regulated cytoskeleton-associated protein (Arc), early growth response 1 (Egr1), and neuronal PAS (Per-ArntSim) domain protein 4 (Npas4) were analysed 1 and 24 h after drug treatments. ResultsPsilocin increased synaptic puncta count and induced Arc expression. The effect to promote synaptogenesis was comparable to ketamine and lithium; ketamine additionally increased PSD-95 puncta count. LSD and DMT didnt induce any significant effect. Interestingly, fluoxetine had no effect on synaptic puncta count, but upregulated Egr1 and Npas4. ConclusionsPsilocin demonstrated a significant neuroplastic effect comparable to that of ketamine and lithium, adding another piece of evidence to its profile as a promising therapeutic agent.

neuroscience↗

bioRxiv2022

Natural language signatures of psilocybin microdosing

Serotonergic psychedelics are being studied as novel treatments for mental health disorders and as facilitators of improved well-being, mental function and creativity. Recent studies have found mixed results concerning the effects of low doses of psychedelics ("microdosing") on these domains. However, microdosing is generally investigated using instruments designed to assess larger doses of psychedelics, which might lack sensitivity and specificity for this purpose. Following a double-blind and placebo-controlled experimental design, we explored natural language as a resource to identify speech produced under the acute effects of psilocybin microdoses, focusing on variables known to be affected by higher doses: verbosity, semantic variability and sentiment scores. Except for semantic variability, these metrics presented significant differences between a typical active microdose of 0.5 g of psilocybin mushrooms and an inactive placebo condition. Moreover, machine learning classifiers trained using these metrics were capable of distinguishing between conditions with high accuracy (AUC{approx}0.8). Our results constitute first proof that low doses of serotonergic psychedelics can be identified from unconstrained natural speech, with potential for widely applicable, affordable, and ecologically valid monitoring of microdosing schedules.

pharmacology and toxicology↗

bioRxiv2021

Microevidence for microdosing with psilocybin mushrooms: a double-blind placebo-controlled study of subjective effects, behavior, creativity, perception, cognition, and brain activity

The use of low sub-hallucinogenic doses of psychedelics ("microdosing") has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies limits our knowledge of microdosing and its effects. Moreover, research conducted in laboratory settings might fail to capture the motivation of individuals engaged in microdosing protocols. We recruited 34 individuals planning to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled design, we investigated the effects of 0.5 g dried mushrooms on subjective experience, behavior, creativity, perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, which could be explained by unblinding. For the other measurements, we observed either null effects or a trend towards cognitive impairment and, in the case of EEG, towards reduced theta band spectral power. Our findings support the possibility that expectation effects underlie at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.

neuroscience↗

bioRxiv2021

Mechanical Metric for Skeletal Biomechanics Derived from Spectral Analysis of Stiffness matrix

A new metric for the quantitative and qualitative evaluation of bone stiffness is introduced. It is based on the spectral decomposition of stiffness matrix computed with finite element method. The here proposed metric is defined as an amplitude rescaled eigenvalues of stiffness matrix. The metric contains unique information on the principal stiffness of bone and reflects both bone shape and material properties. The metric was compared with anthropometrical measures and was tested for sex sensitivity on pelvis bone. Further, the smallest stiffness of pelvis was computed under a certain loading condition and analyzed with respect to sex and direction. The metric complements anthropometrical measures and provides a unique information about the smallest bone stiffness independent from the loading configuration and can be easily computed by state-of-the-art subject specified finite element algorithms.

bioinformatics↗

bioRxiv2021

Bone Mineral Density modelled as a Random Field: a Feasibility Study on Pelvic Bone

Background and ObjectiveCapturing the population variability of bone properties is of paramount importance to biomedical engineering. The aim of the present paper is to describe variability and correlations in bone mineral density with a spatial random field inferred from routine computed tomography data. MethodsRandom fields were simulated by transforming pairwise uncorrelated Gaussian random variables into correlated variables through the spectral decomposition of an age-detrended correlation matrix. The validity of the random field model was demonstrated in the spatiotemporal analysis of bone mineral density. The similarity between the computed tomography samples and those generated via random fields was analyzed with the energy distance metric. ResultsThe random field of bone mineral density was found to be approximately Gaussian/slightly left-skewed/strongly right-skewed at various locations. However, average bone density could be simulated well with the proposed Gaussian random field for which the energy distance, i.e., a measure that quantifies discrepancies between two distribution functions, is convergent with respect to the number of correlation eigenpairs. ConclusionsThe proposed random field model allows the enhancement of computational biomechanical models with variability in bone mineral density, which could increase the usability of the model and provides a step forward in in-silico medicine.

biophysics↗

bioRxiv2020

Shape Morphing Technique Can Accurately Predict Pelvic Bone Landmarks

Diffeomorphic shape registration allows for the seamless geometric alignment of shapes. In this study, we demonstrated the use of a registration algorithm to automatically seed anthropological landmarks on the CT images of the pelvis. We found a high correlation between manually and automatically seeded landmarks. The registration algorithm makes it possible to achieve a high degree of automation with the potential to reduce operator errors in the seeding of anthropological landmarks. The results of this study represent a promising step forward in effectively defining the anthropological measures of the human skeleton. HighlightsO_LIThe clinical CT scan is a feasible alternative to skeletal collections and body donor programs. C_LIO_LIPelvic morphology is complex, sexually dimorphic and is proven to being a good demonstration model for the performance analysis of registration algorithm for automatic landmark seeding. C_LIO_LIThe landmark seeding using registration algorithm can save time and effort in anthropological analysis. C_LI

bioinformatics↗

bioRxiv2018

Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting

IntroductionRecently popular sub-perceptual doses of psychedelic substances such as truffles, referred to as microdosing, allegedly have multiple beneficial effects including creativity and problem solving performance, potentially through targeting serotonergic 5-HT2A receptors and promoting cognitive flexibility, crucial to creative thinking. Nevertheless, enhancing effects of microdosing remain anecdotal, and in the absence of quantitative research on microdosing psychedelics it is impossible to draw definitive conclusions on that matter. Here, our main aim was to quantitatively explore the cognitive-enhancing potential of microdosing psychedelics in healthy adults.\n\nMethodsDuring a microdosing event organized by the Dutch Psychedelic Society, we examined the effects of psychedelic truffles (which were later analyzed to quantify active psychedelic alkaloids) on two creativity-related problem-solving tasks: the Picture Concept Task assessing convergent thinking, and the Alternative Uses Task assessing divergent thinking. A short version of the Ravens Progressive Matrices task assessed potential changes in fluid intelligence. We tested once before taking a microdose and once while the effects were manifested.\n\nResultsWe found that both convergent and divergent thinking performance was improved after a non-blinded microdose, whereas fluid intelligence was unaffected.\n\nConclusionWhile this study provides quantitative support for the cognitive enhancing properties of microdosing psychedelics, future research has to confirm these preliminary findings in more rigorous placebo-controlled study designs. Based on these preliminary results we speculate that psychedelics might affect cognitive metacontrol policies by optimizing the balance between cognitive persistence and flexibility. We hope this study will motivate future microdosing studies with more controlled designs to test this hypothesis.

neuroscience↗