Few-layered graphene increases the response of nociceptive neurons to irritant stimuli.

The unique properties of few-layered graphene (FLG) make it interesting for a variety of applications, including biomedical applications, such as tissue engineering and drug delivery. Although different studies focus on applications in the central nervous system, its interaction with the peripheral nervous system has been so far overlooked. Here, we investigated the effects of exposure to colloidal dispersions of FLG on the sensory neurons of the rat dorsal root ganglia (DRG).

Case Report: Novel biallelic moderately damaging variants in in a patient with cerebellar dysplasia.

Rotatin, encoded by the gene, is a centrosomal protein with multiple, emerging functions, including left-right specification, ciliogenesis, and neuronal migration. Recessive variants in are associated with a neurodevelopmental disorder with microcephaly and malformations of cortical development known as "Microcephaly, short stature, and polymicrogyria with seizures" (MSSP, MIM #614833). Affected individuals show a wide spectrum of clinical manifestations like intellectual disability, poor/absent speech, short stature, microcephaly, and congenital malformations.

T-cell immunophenotype correlations with cortical thickness and white matter microstructure in bipolar disorder.

Background: Inflammation and immunological alterations, such as T-cell and cytokine changes, are implicated in bipolar disorder (BD), with some evidence linking them to brain structural changes (e.g., cortical thickness (CT), gray matter (GM) volume and white matter (WM) microstructure).

Biomolecular Corona of Gold Nanoparticles: The Urgent Need for Strong Roots to Grow Strong Branches.

Gold nanoparticles (GNPs) are largely employed in diagnostics/biosensors and are among the most investigated nanomaterials in biology/medicine. However, few GNP-based nanoformulations have received FDA approval to date, and promising in vitro studies have failed to translate to in vivo efficacy. One key factor is that biological fluids contain high concentrations of proteins, lipids, sugars, and metabolites, which can adsorb/interact with the GNP's surface, forming a layer called biomolecular corona (BMC).

The light-dependent pseudo-capacitive charging of conjugated polymer nanoparticles coupled with the depolarization of the neuronal membrane.

The mechanism underlying visual restoration in blind animal models of retinitis pigmentosa using a liquid retina prosthesis based on semiconductive polymeric nanoparticles is still being debated. Through the application of mathematical models and specific experiments, we developed a coherent understanding of abiotic/biotic coupling, capturing the essential mechanism of photostimulation responsible for nanoparticle-induced retina activation. Our modeling is based on the solution of drift-diffusion and Poisson-Nernst-Planck models in the multi-physics neuron-cleft-nanoparticle-extracellular space domain, accounting for the electro-chemical motion of all the relevant species following photoexcitation.

Conditional knockout of REST/NRSF in excitatory neurons reduces seizure susceptibility to chemical kindling.

The repressor element-1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is an epigenetic master regulator that plays a crucial role during nervous system development and maturation. REST function was originally described during development, where it determines neuronal phenotype. However, recent studies showed that REST participates in several processes in the adult brain, including neuronal plasticity and epileptogenesis.

Low glycemic index diet restrains epileptogenesis in a gender-specific fashion.

Dietary restriction, such as low glycemic index diet (LGID), have been successfully used to treat drug-resistant epilepsy. However, if such diet could also counteract antiepileptogenesis is still unclear. Here, we investigated whether the administration of LGID during the latent pre-epileptic period, prevents or delays the appearance of the overt epileptic phenotype.

Platinum Nanozymes Counteract Photoreceptor Degeneration and Retina Inflammation in a Light-Damage Model of Age-Related Macular Degeneration.

Degeneration of photoreceptors in age-related macular degeneration (AMD) is associated with oxidative stress due to the intense aerobic metabolism of rods and cones that if not properly counterbalanced by endogenous antioxidant mechanisms can precipitate photoreceptor degeneration. In spite of being a priority eye disease for its high incidence in the elderly, no effective treatments for AMD exist. While systemic administration of antioxidants has been unsuccessful in slowing down degeneration, locally administered rare-earth nanoparticles were shown to be effective in preventing retinal photo-oxidative damage.

GFAP serves as a structural element of tunneling nanotubes between glioblastoma cells and could play a role in the intercellular transfer of mitochondria.

Tunneling nanotubes (TNTs) are long F-actin-positive plasma membrane bridges connecting distant cells, allowing the intercellular transfer of cellular cargoes, and are found to be involved in glioblastoma (GBM) intercellular crosstalk. Glial fibrillary acid protein (GFAP) is a key intermediate filament protein of glial cells involved in cytoskeleton remodeling and linked to GBM progression. Whether GFAP plays a role in TNT structure and function in GBM is unknown.

Intercellular crosstalk mediated by tunneling nanotubes between central nervous system cells. What we need to advance.

Long-range intercellular communication between Central Nervous System (CNS) cells is an essential process for preserving CNS homeostasis. Paracrine signaling, extracellular vesicles, neurotransmitters and synapses are well-known mechanisms involved. A new form of intercellular crosstalk mechanism based on Tunneling Nanotubes (TNTs), suggests a new way to understand how neural cells interact with each other in controlling CNS functions.

Nanoscale organization of Ca2.1 splice isoforms at presynaptic terminals: implications for synaptic vesicle release and synaptic facilitation.

The distance between Ca2.1 voltage-gated Ca channels and the Ca sensor responsible for vesicle release at presynaptic terminals is critical for determining synaptic strength. Yet, the molecular mechanisms responsible for a loose coupling configuration of Ca2.

Regulation of dendritic spine length in corticopontine layer V pyramidal neurons by autism risk gene β3 integrin.

The relationship between autism spectrum disorder (ASD) and dendritic spine abnormalities is well known, but it is unclear whether the deficits relate to specific neuron types and brain regions most relevant to ASD. Recent genetic studies have identified a convergence of ASD risk genes in deep layer pyramidal neurons of the prefrontal cortex. Here, we use retrograde recombinant adeno-associated viruses to label specifically two major layer V pyramidal neuron types of the medial prefrontal cortex: the commissural neurons, which put the two cerebral hemispheres in direct communication, and the corticopontine neurons, which transmit information outside the cortex.

Missense mutations in the membrane domain of PRRT2 affect its interaction with Nav1.2 voltage-gated sodium channels.

PRRT2 is a neuronal protein that controls neuronal excitability and network stability by modulating voltage-gated Na channel (Nav). PRRT2 pathogenic variants cause pleiotropic syndromes including epilepsy, paroxysmal kinesigenic dyskinesia and episodic ataxia attributable to loss-of-function pathogenetic mechanism. Based on the evidence that the transmembrane domain of PRRT2 interacts with Nav1.

Modeling PCDH19 clustering epilepsy by Neurogenin 2 induction of patient-derived induced pluripotent stem cells.

Background: Loss of function mutations in PCDH19 gene causes an X-linked, infant-onset clustering epilepsy, associated with intellectual disability and autistic features. The unique pattern of inheritance includes random X-chromosome inactivation, which leads to pathological tissue mosaicism. Females carrying PCDH19 mutations are affected, while males have a normal phenotype.

Catalytic Bioswitch of Platinum Nanozymes: Mechanistic Insights of Reactive Oxygen Species Scavenging in the Neurovascular Unit.

Oxidative stress is known to be the cause of several neurovascular diseases, including neurodegenerative disorders, since the increase of reactive oxygen species (ROS) levels can lead to cellular damage, blood-brain barrier leaking, and inflammatory pathways. Herein, we demonstrate the therapeutic potential of 5 nm platinum nanoparticles (PtNPs) to effectively scavenge ROS in different cellular models of the neurovascular unit. We investigated the mechanism underlying the PtNP biological activities, analyzing the influence of the evolving biological environment during particle trafficking and disclosing a key role of the protein corona, which elicited an effective switch-off of the PtNP catalytic properties, promoting their selective activity.

The impact of pathogenic and artificial mutations on Claudin-5 selectivity from molecular dynamics simulations.

Tight-junctions (TJs) are multi-protein complexes between adjacent endothelial or epithelial cells. In the blood-brain-barrier (BBB), they seal the paracellular space and the Claudin-5 (Cldn5) protein forms their backbone. Despite the fundamental role in brain homeostasis, little is known on Cldn5-based TJ assemblies.

Biomechanics, motor control and dynamic models of the soft limbs of the octopus and other cephalopods.

Muscular hydrostats are organs composed entirely of packed arrays of incompressible muscles and lacking any skeletal support. Found in both vertebrates and invertebrates, they are of great interest for comparative biomechanics from engineering and evolutionary perspectives. The arms of cephalopods (e.

The intramembrane COOH-terminal domain of PRRT2 regulates voltage-dependent Na channels.

Proline-rich transmembrane protein 2 (PRRT2) is the single causative gene for pleiotropic paroxysmal syndromes, including epilepsy, kinesigenic dyskinesia, episodic ataxia, and migraine. PRRT2 is a neuron-specific type-2 membrane protein with a COOH-terminal intramembrane domain and a long proline-rich NH-terminal cytoplasmic region. A large array of experimental data indicates that PRRT2 is a neuron stability gene that negatively controls intrinsic excitability by regulating surface membrane localization and biophysical properties of voltage-dependent Na channels Nav1.

Interactions of Graphene Oxide and Few-Layer Graphene with the Blood-Brain Barrier.

Thanks to their biocompatibility and high cargo capability, graphene-based materials (GRMs) might represent an ideal brain delivery system. The capability of GRMs to reach the brain has mainly been investigated and has highlighted some controversy. Herein, we employed two BBB models of increasing complexity to investigate the bionano interactions with graphene oxide (GO) and few-layer graphene (FLG): a 2D murine Transwell model, followed by a 3D human multicellular assembloid, to mimic the complexity of the architecture and intercellular crosstalk.

The tetraspanin TSPAN5 regulates AMPAR exocytosis by interacting with the AP4 complex.

Intracellular trafficking of AMPA receptors is a tightly regulated process which involves several adaptor proteins, and is crucial for the activity of excitatory synapses both in basal conditions and during synaptic plasticity. We found that, in rat hippocampal neurons, an intracellular pool of the tetraspanin TSPAN5 promotes exocytosis of AMPA receptors without affecting their internalisation. TSPAN5 mediates this function by interacting with the adaptor protein complex AP4 and Stargazin and possibly using recycling endosomes as a delivery route.