Impact of graphene nanosheets on primary astrocytes

Impact of graphene nanosheets on primary astrocyte

Erratum: Photoluminescence and Morphology of Alq[sub 3] Films and Four-Components Model [J. Electrochem. Soc., 154, J217 (2007)]

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Effect of Continuous Touch on Brain Functional Connectivity Is Modified by the Operator’s Tactile Attention

Touch has been always regarded as a powerful communication channel playing a key role in governing our emotional wellbeing and possibly perception of self. Several studies demonstrated that the stimulation of C-tactile afferent fibers, essential neuroanatomical elements of affective touch, activates specific brain areas and the activation pattern is influenced by subject’s attention. However, no research has investigated how the cognitive status of who is administering the touch produces changes in brain functional connectivity of touched subjects. In this functional magnetic resonance imaging (fMRI) study, we investigated brain connectivity while subjects were receiving a static touch by an operator engaged in either a tactile attention or auditory attention task. This randomized-controlled single-blinded study enrolled 40 healthy right-handed adults and randomly assigned to either the operator tactile attention (OTA) or the operator auditory attention (OAA) group. During the five fMRI resting-state runs, the touch was delivered while the operator focused his attention either: (i) on the tactile perception from his hands (OTA group); or (ii) on a repeated auditory stimulus (OAA group). Functional connectivity analysis revealed that prolonged sustained static touch applied by an operator engaged with focused tactile attention produced a significant increase of anticorrelation between posterior cingulate cortex (PCC-seed) and right insula (INS) as well as right inferior-frontal gyrus but these functional connectivity changes are markedly different only after 15 min of touching across the OTA and OAA conditions. Interestingly, data also showed anticorrelation between PCC and left INS with a distinct pattern over time. Indeed, the PCC-left INS anticorrelation is showed to start and end earlier compared to that of PCC-right INS. Taken together, the results of this study showed that if a particular cognitive status of the operator is sustained over time, it is able to elicit significant effects on the subjects’ functional connectivity patterns involving cortical areas processing the interoceptive and attentional value of touch

Neuronal hyperactivity causes Na+/H+ exchanger-induced extracellular acidification at active synapses

Extracellular pH impacts on neuronal activity, which is in turn an important determinant of extracellular H+ concentration. The aim of this study is to describe the spatio-temporal dynamics of extracellular pH at synaptic sites during neuronal hyperexcitability. To address this issue we created ex.E2GFP, a membrane-targeted extracellular ratiometric pH indicator exquisitely sensitive to acidic shifts. By monitoring ex.E2GFP fluorescence in real time in primary cortical neurons we were able to quantify pH fluctuations during network hyperexcitability induced by convulsant drugs or high frequency electrical stimulation. Sustained hyperactivity caused a pH decrease that was reversible upon silencing of neuronal activity and localized to active synapses. This acidic shift was not attributable to the outflow of synaptic vesicle protons into the cleft nor to the activity of membrane-exposed H+-vATPase, but rather to the activity of the Na+/H+-exchanger. Our data demonstrate that extracellular synaptic pH shifts take place during epileptic-like activity of neural cultures, underlying the strict links existing between synaptic activity and synaptic pH. This evidence may contribute to the understanding of the physio-pathological mechanisms associated with hyperexcitability in the epileptic brain

Interfacing Graphene-Based Materials With Neural Cells

The scientific community has witnessed an exponential increase in the applications of graphene and graphene-based materials in a wide range of fields, from engineering to electronics to biotechnologies and biomedical applications. For what concerns neuroscience, the interest raised by these materials is two-fold. On one side, nanosheets made of graphene or graphene derivatives (graphene oxide, or its reduced form) can be used as carriers for drug delivery. Here, an important aspect is to evaluate their toxicity, which strongly depends on flake composition, chemical functionalization and dimensions. On the other side, graphene can be exploited as a substrate for tissue engineering. In this case, conductivity is probably the most relevant amongst the various properties of the different graphene materials, as it may allow to instruct and interrogate neural networks, as well as to drive neural growth and differentiation, which holds a great potential in regenerative medicine. In this review, we try to give a comprehensive view of the accomplishments and new challenges of the field, as well as which in our view are the most exciting directions to take in the immediate future. These include the need to engineer multifunctional nanoparticles (NPs) able to cross the blood-brain-barrier to reach neural cells, and to achieve on-demand delivery of specific drugs. We describe the state-of-the-art in the use of graphene materials to engineer three-dimensional scaffolds to drive neuronal growth and regeneration in vivo, and the possibility of using graphene as a component of hybrid composites/multi-layer organic electronics devices. Last but not least, we address the need of an accurate theoretical modeling of the interface between graphene and biological material, by modeling the interaction of graphene with proteins and cell membranes at the nanoscale, and describing the physical mechanism(s) of charge transfer by which the various graphene materials can influence the excitability and physiology of neural cells

Graphene Oxide Upregulates the Homeostatic Functions of Primary Astrocytes and Modulates Astrocyte-to-Neuron Communication

Graphene-based materials are the focus of intense research efforts to devise novel theranostic strategies for targeting the central nervous system. In this work, we have investigated the consequences of long-term exposure of primary rat astrocytes to pristine graphene (GR) and graphene oxide (GO) flakes. We demonstrate that GR/GO interfere with a variety of intracellular processes as a result of their internalization through the endolysosomal pathway. Graphene-exposed astrocytes acquire a more differentiated morphological phenotype associated with extensive cytoskeletal rearrangements. Profound functional alterations are induced by GO internalization, including the upregulation of inward-rectifying K+ channels and of Na+-dependent glutamate uptake, which are linked to the astrocyte capacity to control the extracellular homeostasis. Interestingly, GO-pretreated astrocytes promote the functional maturation of co-cultured primary neurons by inducing an increase in intrinsic excitability and in the density of GABAergic synapses. The results indicate that graphene nanomaterials profoundly affect astrocyte physiology in vitro with consequences for neuronal network activity. This work supports the view that GO-based materials could be of great interest to address pathologies of the central nervous system associated with astrocyte dysfunctions

Phase transitions in thermally annealed films of Alq₃

Organic light emitting devices have been so very much improved lately that they are being widely applied for displays and lighting. Among many improving technologies, annealing processes in different atmospheres affect greatly their performance, for instance when the active material is the small molecule Alq3. In particular, a significant increase of the photoluminescence is observed in thin films of this molecule between 150 and 180 °C, before the physical destruction of the films occurs at higher temperatures. This phenomenon is attributed to a phase transition towards a novel morphological aggregation of the molecules in the film, which proved to be a much improved optical material for luminescent applications, and which seems common to other molecules as well

A Dedicated Tool for Presurgical Mapping of Brain Tumors and Mixed-Reality Navigation During Neurosurgery

Brain tumor surgery requires a delicate tradeoff between complete removal of neoplastic tissue while minimizing loss of brain function. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) have emerged as valuable tools for non-invasive assessment of human brain function and are now used to determine brain regions that should be spared to prevent functional impairment after surgery. However, image analysis requires different software packages, mainly developed for research purposes and often difficult to use in a clinical setting, preventing large-scale diffusion of presurgical mapping. We developed a specialized software able to implement an automatic analysis of multimodal MRI presurgical mapping in a single application and to transfer the results to the neuronavigator. Moreover, the imaging results are integrated in a commercially available wearable device using an optimized mixed-reality approach, automatically anchoring 3-dimensional holograms obtained from MRI with the physical head of the patient. This will allow the surgeon to virtually explore deeper tissue layers highlighting critical brain structures that need to be preserved, while retaining the natural oculo-manual coordination. The enhanced ergonomics of this procedure will significantly improve accuracy and safety of the surgery, with large expected benefits for health care systems and related industrial investors

An Increase in Membrane Cholesterol by Graphene Oxide Disrupts Calcium Homeostasis in Primary Astrocytes

The use of graphene nanomaterials (GNMs) for biomedical applications targeted to the central nervous system is exponentially increasing, although precise information on their effects on brain cells is lacking. In this work, the molecular changes induced in cortical astrocytes by few-layer graphene (FLG) and graphene oxide (GO) flakes are addressed. The results show that exposure to FLG/GO does not affect cell viability or proliferation. However, proteomic and lipidomic analyses unveil alterations in several cellular processes, including intracellular Ca2+ ([Ca2+ ]i ) homeostasis and cholesterol metabolism, which are particularly intense in cells exposed to GO. Indeed, GO exposure impairs spontaneous and evoked astrocyte [Ca2+ ]i signals and induces a marked increase in membrane cholesterol levels. Importantly, cholesterol depletion fully rescues [Ca2+ ]i dynamics in GO-treated cells, indicating a causal relationship between these GO-mediated effects. The results indicate that exposure to GNMs alters intracellular signaling in astrocytes and may impact astrocyte-neuron interactions