Utilización de campos magnéticos y nanopartículas magnéticas para la orientación de células neuronales

Este Trabajo Fin de Grado se centra en el estudio de la capacidad de nanopartículas de magnetita (MNPs) biocompatibles de orientar células cuando éstas las ingieren y son sometidas a un campo magnético estático. Se pretende desarrollar una configuración de campo que optimice la fuerza magnética que actúa sobre estas MNPs absorbidas. El papel de la fuerza es orientar los organismos celulares. Por tratarse de componentes del tejido nervioso, las células empleadas poseen unas ramificaciones cortas e irregulares en el cuerpo celular, en cuya observación nos centraremos para hablar de esa orientación. Tras un estudio teórico previo de los parámetros a optimizar de la fuerza, se simulará el campo magnético mediante un algoritmo de elementos finitos (FEMM). Este método proporcionará resultados numéricos de los diseños de perfiles magnéticos realizados, que servirán como modelo para la construcción de un aplicador de imanes de NdFeB. Se busca reproducir en el laboratorio del INA los valores simulados y terminar haciendo un análisis estadístico del ángulo de la orientación de las células neuronales con el campo magnético, para concluir que tal orientación existe

Exploring semantic verbal fluency patterns and their relationship to age and Alzheimer's disease in adults with Down syndrome

Introduction: Adults with Down syndrome (DS) are at ultra-high risk of developing Alzheimer's disease (AD), characterized by poor episodic memory and semantic fluency in the preclinical phase in the general population. We explored semantic fluency performance in DS and its relationship to age, AD, and blood biomarkers. Methods: A total of 302 adults with DS at baseline and 87 at follow-up from the London Down Syndrome Consortium cohort completed neuropsychological assessments. Blood biomarkers were measured with the single molecule array technique in a subset of 94 participants. Results: Poorer verbal fluency performance was observed as age increases. Number of correct words declined in those with AD compared to those without over 2 years and was negatively correlated with neurofilament light (r = –0.37, P =.001) and glial fibrillary acidic protein (r = –0.31, P =.012). Discussion: Semantic fluency may be useful as an early indicator of cognitive decline and provide additional information on AD-related change, showing associations with biomarkers in DS

COVIDiSTRESS diverse dataset on psychological and behavioural outcomes one year into the COVID-19 pandemic

During the onset of the COVID-19 pandemic, the COVIDiSTRESS Consortium launched an open-access global survey to understand and improve individuals’ experiences related to the crisis. A year later, we extended this line of research by launching a new survey to address the dynamic landscape of the pandemic. This survey was released with the goal of addressing diversity, equity, and inclusion by working with over 150 researchers across the globe who collected data in 48 languages and dialects across 137 countries. The resulting cleaned dataset described here includes 15,740 of over 20,000 responses. The dataset allows cross-cultural study of psychological wellbeing and behaviours a year into the pandemic. It includes measures of stress, resilience, vaccine attitudes, trust in government and scientists, compliance, and information acquisition and misperceptions regarding COVID-19. Open-access raw and cleaned datasets with computed scores are available. Just as our initial COVIDiSTRESS dataset has facilitated government policy decisions regarding health crises, this dataset can be used by researchers and policy makers to inform research, decisions, and policy. © 2022, The Author(s).U.S. Department of Education, ED: P031S190304; Texas A and M International University, TAMIU; National Research University Higher School of Economics, ВШЭThe COVIDiSTRESS Consortium would like to acknowledge the contributions of friends and collaborators in translating and sharing the COVIDiSTRESS survey, as well as the study participants. Data analysis was supported by Texas A&M International University (TAMIU) Research Grant, TAMIU Act on Ideas, and the TAMIU Advancing Research and Curriculum Initiative (TAMIU ARC) awarded by the US Department of Education Developing Hispanic-Serving Institutions Program (Award # P031S190304). Data collection by Dmitrii Dubrov was supported within the framework of the Basic Research Program at HSE University, RF

Action potential alterations induced by single neuron mechanical loading

Since the 1940s, an extensive body of empirical evidence has been gathered about non-electrical alterations accompanying the voltage depolarisation of a neuron during the generation and propagation of an action potential (AP). The prevailing traditional electrochemical models do not account for these changes, and are as a result incomplete. At the same time, multiple research programmes have demonstrated how ultrasound (US) -a mechanical wave- can non-invasively and reversibly mechanically perturb neuronal functions. Strikingly, the mechanisms of action remain largely unknown. In this framework, this thesis takes the approach to focus on single cell studies to better understand and exploit the multiphysics of the neuronal action potential and aims at studying the effects of direct mechanical loadings on the shape and dynamics of the neuronal signal. First, a multiphysics platform combining nanoindentation and patch clamp systems, assembled in an inverted microscope, is designed to simultaneously measure mechanical and electrophysiological properties of single neurons while imaging the cell morphology. The functionality of the setup is first used to provide a full characterisation of the neuronal cell line chosen here, i.e., dorsal root ganglion-derived cells, and then to quantify the alterations in the magnitude and dynamics of single neuron spontaneous APs before, during and after quasi-static and dynamic mechanical loadings over a wide range of frequencies (up to 1 MHz). Quasi-static indentation tests show transiently smaller, wider and slower depolarising APs during compressions within the cell's linear viscoelastic regime, which translates in slower AP dynamics, as well as sustained hyperpolarised cells with longer repolarisation rates after the indentation. Dynamic loading results, instead, show narrower APs with shorter depolarisation and repolarisation phases, i.e., faster induced AP dynamics, at increasing frequencies, particularly for stimulations at around 1 MHz. In addition, results at this frequency are more evident after indentation, hinting at a cumulative or lagged effect of mechanical stimulation at US frequencies. These observations are attributed to the stiffening of the membrane and membrane cortex as a result of the mechanical oscillations, as well as potentially related phase state alterations. Taken together, these findings highlight the importance of mechanical cues in shaping the neuronal AP, and the often overlooked role of the membrane and its mechanical properties in determining cell functionality. In particular, the promoted faster AP dynamics that emerge after high frequency mechanical oscillations suggest a potential mechanism of US neuromodulation and support the assumption that direct mechanical cellular agitations induced by US stimulation protocols assist the observed neuromodulatory effects.</p

Single cell electrophysiological alterations under dynamic loading at ultrasonic frequencies

The use of ultrasound as a non-invasive means to modulate neuronal electrophysiological signals in experimental in vivo and in vitro models has recently been gaining momentum. Paradoxically, the intrinsic mechanisms linking high-frequency minute mechanical vibrations to electrophysiological alterations at the cellular scale are yet to be identified in this context. To this end, this work combines patch clamp and nanoindentation to study the action potential alterations induced by direct mechanical vibrations at ultrasonic frequencies of dorsal root ganglion-derived neuronal single cells. The characteristics of the action potentials are studied under oscillatory shear loadings of 25 and 50 nm displacement amplitudes at frequencies ranging from 250 kHz to 1 MHz. Results show significantly narrower action potentials, with faster depolarisations and shorter rising and falling phases when induced after 1 MHz. The faster action potential dynamics appearing once the oscillation is removed points towards a cumulative or lagged effect of mechanical stimulation at ultrasonic frequencies, also observed in ultrasound neuromodulation studies. It is hypothesised here that this action potential modulation arises as a consequence of remarkable membrane properties changes induced above a threshold frequency, situated between 370 kHz and 960 kHz, and possibly related to membrane stiffening and membrane phase state alterations. These observations demonstrate the ability of mechanical cues at the cellular level to modify the neuronal signal and assert the importance of the direct mechanical vibrations induced by ultrasound stimulation protocols in assisting the observed neuromodulatory effects

Action potential alterations induced by single F11 neuronal cell loading

Several research programmes have demonstrated how Transcranial Ultrasound Stimulation (TUS) can non-invasively and reversibly mechanically perturb neuronal functions. However, the mechanisms through which such reversible and a priori non-damaging behaviour can be observed remain largely unknown. While several TUS protocols have demonstrated motor and behavioural alterations in in vivo models, in vitro studies remain scarce. In particular, an experimental framework able to load mechanically an individual neuron in a controlled manner and simultaneously measure the generation and evolution of action potentials before, during and after such load, while allowing for direct microscopy, has not been successfully proposed. To this end, we herein present a multiphysics setup combining nanoindentation and patch clamp systems, assembled in an inverted microscope for simultaneous bright-field or fluorescence imaging. We evaluate the potential of the platform with a set of experiments in which single dorsal root ganglion-derived neuronal cell bodies are compressed while their spontaneous activity is recorded. We show that these transient quasi-static mechanical loads reversibly affect the amplitude and rate of change of the neuronal action potentials, which are smaller and slower upon indentation, while irreversibly altering other features. The ability to simultaneously image, mechanically and electrically manipulate and record single cells in a perturbed mechanical environment makes this system particularly suitable for studying the multiphysics of the brain at the cell level

Voltage-driven alterations to neuron viscoelasticity

Background: The consideration of neurons as coupled mechanical-electrophysiological systems is supported by a growing body of experimental evidence, including observations that cell membranes mechanically deform during the propagation of an action potential. However, the short-term (seconds to minutes) influence of membrane voltage on the mechanical properties of a neuron at the single-cell level remains unknown. Materials and Methods: Here, we use microscale dynamic mechanical analysis to demonstrate that changes in membrane potential induce changes in the mechanical properties of individual neurons. We simultaneously measured the membrane potential and mechanical properties of individual neurons through a multiphysics single-cell setup. Membrane voltage of a single neuron was measured through whole-cell patch clamp. The mechanical properties of the same neuron were measured through a nanoindenter, which applied a dynamic indentation to the neuron at different frequencies. Results: Neuronal storage and loss moduli were lower for positive voltages than negative voltages. Conclusion: The observed effects of membrane voltage on neuron mechanics could be due to piezoelectric or flexoelectric effects and altered ion distributions under the applied voltage. Such effects could change cell mechanics by changing the intermolecular interactions between ions and the various biomolecules within the membrane and cytoskeleton