Investigations of Astrocyte Calcium Signaling and Imaging with Classical and Nonclassical Light.

The application of light in studying and influencing cellular behavior with improved temporal and spatial resolution remains a key objective in fields such as chemistry, physics, medicine, and engineering. In the brain, nonexcitable cells called astrocytes play essential roles in regulating homeostasis and cognitive function through complex calcium signaling pathways. Understanding these pathways is vital for deciphering brain physiology and neurological disorders like Parkinson's and Alzheimer's.

Graphene oxide electrodes enable electrical stimulation of distinct calcium signalling in brain astrocytes.

Astrocytes are responsible for maintaining homoeostasis and cognitive functions through calcium signalling, a process that is altered in brain diseases. Current bioelectronic tools are designed to study neurons and are not suitable for controlling calcium signals in astrocytes. Here, we show that electrical stimulation of astrocytes using electrodes coated with graphene oxide and reduced graphene oxide induces respectively a slow response to calcium, mediated by external calcium influx, and a sharp one, exclusively due to calcium release from intracellular stores.

Aquaporin-4 and transient receptor potential vanilloid 4 balance in early postnatal neurodevelopment.

In the adult brain, the water channel aquaporin-4 (AQP4) is expressed in astrocyte endfoot, in supramolecular assemblies, called "Orthogonal Arrays of Particles" (OAPs) together with the transient receptor potential vanilloid 4 (TRPV4), finely regulating the cell volume. The present study aimed at investigating the contribution of AQP4 and TRPV4 to CNS early postnatal development using WT and AQP4 KO brain and retina and neuronal stem cells (NSCs), as an in vitro model of astrocyte differentiation. Western blot analysis showed that, differently from AQP4 and the glial cell markers, TRPV4 was downregulated during CNS development and NSC differentiation.

Innovative solutions for disease management.

The increasing prevalence of chronic diseases is a driver for emerging big data technologies for healthcare including digital platforms for data collection, systems for active patient engagement and education, therapy specific predictive models, optimized patient pathway models. Powerful bioelectronic medicine tools for data collection, analysis and visualization allow for joint processing of large volumes of heterogeneous data, which in turn can produce new insights about patient outcomes and alternative interpretations of clinical patterns that can lead to implementation of optimized clinical decisions and clinical patient pathway by healthcare professionals.With this perspective, we identify innovative solutions for disease management and evaluate their impact on patients, payers and society, by analyzing their impact in terms of clinical outcomes (effectiveness, safety, and quality of life) and economic outcomes (cost-effectiveness, savings, and productivity).

AQP4-independent TRPV4 modulation of plasma membrane water permeability.

Despite of the major role of aquaporin (AQP) water channels in controlling transmembrane water fluxes, alternative ways for modulating water permeation have been proposed. In the Central Nervous System (CNS), Aquaporin-4 (AQP4) is reported to be functionally coupled with the calcium-channel Transient-Receptor Potential Vanilloid member-4 (TRPV4), which is controversially involved in cell volume regulation mechanisms and water transport dynamics. The present work aims to investigate the selective role of TRPV4 in regulating plasma membrane water permeability in an AQP4-independent way.

The emerging science of Glioception: Contribution of glia in sensing, transduction, circuit integration of interoception.

Interoception is the process by which the nervous system regulates internal functions to achieve homeostasis. The role of neurons in interoception has received considerable recent attention, but glial cells also contribute. Glial cells can sense and transduce signals including osmotic, chemical, and mechanical status of extracellular milieu.

Polyaniline nano-needles into electrospun bio active fibres support astrocyte response.

Recent studies have proposed that the bioelectrical response of glial cells, called astrocytes, currently represents a key target for neuroregenerative purposes. Here, we propose the fabrication of electrospun nanofibres containing gelatin and polyaniline (PANi) synthesized in the form of nano-needles (PnNs) as electrically conductive scaffolds to support the growth and functionalities of primary astrocytes. We report a fine control of the morphological features in terms of fibre size and spatial distribution and fibre patterning, random or aligned fibre organization, as revealed by SEM- and TEM-supported image analysis.

Electroconductive and injectable hydrogels based on gelatin and PEDOT:PSS for a minimally invasive approach in nervous tissue regeneration.

This work describes the development of electroconductive hydrogels as injectable matrices for neural tissue regeneration by exploiting a biocompatible conductive polymer - poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) - combined with a biomimetic polymer network made of gelatin. Our approach involved also genipin - a natural cross-linking agent - to promote gelation of gelatin networks embedding PEDOT:PSS. The achieved results suggest that physical-chemical properties of the resulting hydrogels, like impedance, gelation time, mechanical properties, swelling and degradation in physiological conditions, can be finely tuned by the amount of PEDOT:PSS and genipin used in the formulation.

Cell Volume Regulation Mechanisms in Differentiated Astrocytes.

Background/aims: The ability of astrocytes to control extracellular volume homeostasis is critical for brain function and pathology. Uncovering the mechanisms of cell volume regulation by astrocytes will be important for identifying novel therapeutic targets for neurological conditions, such as those characterized by imbalances to hydro saline challenges (as in edema) or by altered cell volume regulation (as in glioma). One major challenge in studying the astroglial membrane channels involved in volume homeostasis in cell culture model systems is that the expression patterns of these membrane channels do not resemble those observed in vivo.

Graphene glial-interfaces: challenges and perspectives.

Graphene nanosheets are mechanically strong but flexible, electrically conductive and bio-compatible. Thus, due to these unique properties, they are being intensively studied as materials for the next generation of neural interfaces. Most of the literature focused on optimizing the interface between these materials and neurons.

Structural and functional properties of astrocytes on PCL based electrospun fibres.

Increasing evidences are demonstrating that structural and functional properties of non-neuronal brain cells, called astrocytes, such as those of cytoskeleton and of ion channels, are critical for brain physiology. Also, changes in astrocytes structure and function concur to and might determine the outcome of neuronal damage in acute neurological conditions or of chronic disease. Thus, the design and engineering of biomaterials that can drive the structural and functional properties of astrocytes is of growing interest for neuroregenerative medicine.

Glial Interfaces: Advanced Materials and Devices to Uncover the Role of Astroglial Cells in Brain Function and Dysfunction.

Research over the past four decades has highlighted the importance of certain brain cells, called glial cells, and has moved the neurocentric vision of structure, function, and pathology of the nervous system toward a more holistic perspective. In this view, the demand for technologies that are able to target and both selectively monitor and control glial cells is emerging as a challenge across neuroscience, engineering, chemistry, and material science. Frequently neglected or marginally considered as a barrier to be overcome between neural implants and neuronal targets, glial cells, and in particular astrocytes, are increasingly considered as active players in determining the outcomes of device implantation.

A Glial-Silicon Nanowire Electrode Junction Enabling Differentiation and Noninvasive Recording of Slow Oscillations from Primary Astrocytes.

The correct human brain function is dependent on the activity of non-neuronal cells called astrocytes. The bioelectrical properties of astrocytes in vitro do not closely resemble those displayed in vivo and the former are incapable of generating action potential; thus, reliable approaches in vitro for noninvasive electrophysiological recording of astrocytes remain challenging for biomedical engineering. Here it is found that primary astrocytes grown on a device formed by a forest of randomly oriented gold coated-silicon nanowires, resembling the complex structural and functional phenotype expressed by astrocytes in vivo.

Stimulation of water and calcium dynamics in astrocytes with pulsed infrared light.

Astrocytes are non-neuronal cells that govern the homeostatic regulation of the brain through ions and water transport, and Ca -mediated signaling. As they are tightly integrated into neural networks, label-free tools that can modulate cell function are needed to evaluate the role of astrocytes in brain physiology and dysfunction. Using live-cell fluorescence imaging, pharmacology, electrophysiology, and genetic manipulation, we show that pulsed infrared light can modulate astrocyte function through changes in intracellular Ca and water dynamics, providing unique mechanistic insight into the effect of pulsed infrared laser light on astroglial cells.

Electrical Stimulation by an Organic Transistor Architecture Induces Calcium Signaling in Nonexcitable Brain Cells.

Organic bioelectronics have a huge potential to generate interfaces and devices for the study of brain functions and for the therapy of brain pathologies. In this context, increasing efforts are needed to develop technologies for monitoring and stimulation of nonexcitable brain cells, called astrocytes. Astroglial calcium signaling plays, indeed, a pivotal role in the physiology and pathophysiology of the brain.

LRRC8A is essential for swelling-activated chloride current and for regulatory volume decrease in astrocytes.

Consolidated evidence indicates that astroglial cells are critical in the homeostatic regulation of cellular volume by means of ion channels and aquaporin-4. Volume-regulated anion channel (VRAC) is the chloride channel that is activated upon cell swelling and critically contributes to cell volume regulation in astrocytes. The molecular identity of VRAC has been recently defined, revealing that it belongs to the leucine-rich repeat-containing 8 (LRRC8) protein family.

A Nanoscale Interface Promoting Molecular and Functional Differentiation of Neural Cells.

Potassium channels and aquaporins expressed by astrocytes are key players in the maintenance of cerebral homeostasis and in brain pathophysiologies. One major challenge in the study of astrocyte membrane channels in vitro, is that their expression pattern does not resemble the one observed in vivo. Nanostructured interfaces represent a significant resource to control the cellular behaviour and functionalities at micro and nanoscale as well as to generate novel and more reliable models to study astrocytes in vitro.

A self-assembled lysinated perylene diimide film as a multifunctional material for neural interfacing.

We report the design, synthesis and structure-property investigation of a new perylene diimide material (PDI-Lys) bearing lysine end substituents. Water processed films of PDI-Lys were prepared and their self-assembly, morphology and electrical properties in both inert and air environments were theoretically and experimentally investigated. With the aim of evaluating the potential of PDI-Lys as a biocompatible and functional neural interface for organic bioelectronic applications, its electrochemical impedance as well as the adhesion and viability properties of primary neurons on the PDI-Lys films were studied.

Silk fibroin film from golden-yellow Bombyx mori is a biocomposite that contains lutein and promotes axonal growth of primary neurons.

The use of doped silk fibroin (SF) films and substrates from Bombyx mori cocoons for green nanotechnology and biomedical applications has been recently highlighted. Cocoons from coloured strains of B. mori, such as Golden-Yellow, contain high levels of pigments that could have a huge potential for the fabrication of SF based biomaterials targeted to photonics, optoelectronics and neuroregenerative medicine.

Androgen Receptor Targeted Conjugate for Bimodal Photodynamic Therapy of Prostate Cancer in Vitro.

Prostate cancer (PC) represents the most common type of cancer among males and is the second leading cause of cancer death in men in Western society. Current options for PC therapy remain unsatisfactory, since they often produce uncomfortable long-term side effects, such as impotence (70%) and incontinence (5-20%) even in the first stages of the disease. Light-triggered therapies, such as photodynamic therapy, have the potential to provide important advances in the treatment of localized and partially metastasized prostate cancer.

A lysinated thiophene-based semiconductor as a multifunctional neural bioorganic interface.

Lysinated molecular organic semiconductors are introduced as valuable multifunctional platforms for neural cells growth and interfacing. Cast films of quaterthiophene (T4) semiconductor covalently modified with lysine-end moieties (T4Lys) are fabricated and their stability, morphology, optical/electrical, and biocompatibility properties are characterized. T4Lys films exhibit fluorescence and electronic transport as generally observed for unsubstituted oligothiophenes combined to humidity-activated ionic conduction promoted by the charged lysine-end moieties.

A new gating site in human aquaporin-4: Insights from molecular dynamics simulations.

Aquaporin-4 (AQP4) is the predominant water channel in different organs and tissues. An alteration of its physiological functioning is responsible for several disorders of water regulation and, thus, is considered an attractive target with a promising therapeutic and diagnostic potential. Molecular dynamics (MD) simulations performed on the AQP4 tetramer embedded in a bilayer of lipid molecules allowed us to analyze the role of spontaneous fluctuations occurring inside the pore.

A nanostructured conductive bio-composite of silk fibroin-single walled carbon nanotubes.

Silk fibroin (SF), a protein core fibre from the silkworm Bombyx mori, has huge potential to become a sustainable, biocompatible, and biodegradable material platform that can pave the way towards the replacement of plastic in the fabrication of bio-derived materials for a variety of technological and biomedical applications. SF has remarkable mechanical flexibility, controllable biodegradability, biocompatibility and is capable of drug/doping inclusion, stabilization and release. However, the dielectric properties of SF limit its potential as a direct bioelectronic interface in biomedical devices intended to control the bioelectrical activity of the cell for regenerative purposes.