Conditional Knockout of Neurexins Alters the Contribution of Calcium Channel Subtypes to Presynaptic Ca Influx.

Presynaptic Ca influx through voltage-gated Ca channels (VGCCs) is a key signal for synaptic vesicle release. Synaptic neurexins can partially determine the strength of transmission by regulating VGCCs. However, it is unknown whether neurexins modulate Ca influx via all VGCC subtypes similarly.

Deletion of β-Neurexins in Mice Alters the Distribution of Dense-Core Vesicles in Presynapses of Hippocampal and Cerebellar Neurons.

Communication between neurons through synapses includes the release of neurotransmitter-containing synaptic vesicles (SVs) and of neuromodulator-containing dense-core vesicles (DCVs). Neurexins (Nrxns), a polymorphic family of cell surface molecules encoded by three genes in vertebrates (Nrxn1-3), have been proposed as essential presynaptic organizers and as candidates for cell type-specific or even synapse-specific regulation of synaptic vesicle exocytosis. However, it remains unknown whether Nrxns also regulate DCVs.

In Vitro Compression Model for Orthodontic Tooth Movement Modulates Human Periodontal Ligament Fibroblast Proliferation, Apoptosis and Cell Cycle.

Human Periodontal Ligament Fibroblasts (hPDLF), as part of the periodontal apparatus, modulate inflammation, regeneration and bone remodeling. Interferences are clinically manifested as attachment loss, tooth loosening and root resorption. During orthodontic tooth movement (OTM), remodeling and adaptation of the periodontium is required in order to enable tooth movement.

Mechanical strength and hydrostatic testing of VIVO adhesive in sutureless microsurgical anastomoses: an ex vivo study.

Conventional anastomoses with interrupted sutures are challenging and inevitably associated with trauma to the vessel walls. The goal of this study was to evaluate a novel alternative adhesive-based suture-free anastomosis technique that uses an intraluminal stent. Overall, 120 porcine coronary vessels were analyzed in an ex vivo model and were examined for their mechanical (n = 20 per cohort) and hydrostatic strength (n = 20 per cohort).

Endogenous β-neurexins on axons and within synapses show regulated dynamic behavior.

Neurexins are key organizer molecules that regulate synaptic function and are implicated in autism and schizophrenia. β-neurexins interact with numerous cell adhesion and receptor molecules, but their neuronal localization remains elusive. Using single-molecule tracking and high-resolution microscopy to detect neurexin1β and neurexin3β in primary hippocampal neurons from knockin mice, we demonstrate that endogenous β-neurexins are present in fewer than half of excitatory and inhibitory synapses.

Presynaptic αδ subunits are key organizers of glutamatergic synapses.

In nerve cells the genes encoding for αδ subunits of voltage-gated calcium channels have been linked to synaptic functions and neurological disease. Here we show that αδ subunits are essential for the formation and organization of glutamatergic synapses. Using a cellular αδ subunit triple-knockout/knockdown model, we demonstrate a failure in presynaptic differentiation evidenced by defective presynaptic calcium channel clustering and calcium influx, smaller presynaptic active zones, and a strongly reduced accumulation of presynaptic vesicle-associated proteins (synapsin and vGLUT).

Implementation of a fully digital histology course in the anatomical teaching curriculum during COVID-19 pandemic.

Background: During the COVID-19 pandemic, many medical schools are forced to switch courses of the mandatory curriculum to online teaching formats. However, little information about feasibility and effectiveness is available yet about distance teaching in anatomy. The aim of this study was to evaluate the implementation of a histology course previously taught in a classroom setting into an online-only format based on video conference software.

Gene expression and phosphorylation of ERK and AKT are regulated depending on mechanical force and cell confluence in murine cementoblasts.

Cementoblasts, located on the tooth root surface covered with cementum, are considered to have tooth protecting abilities. They prevent tissue damage and secure teeth anchorage inside the periodontal ligament during mechanical stress. However, the involvement of cementoblasts in mechanical compression induced periodontal remodeling needs to be identified and better understood.

Selection and validation of reference genes by RT-qPCR for murine cementoblasts in mechanical loading experiments simulating orthodontic forces in vitro.

Different structures and cell types of the periodontium respond to orthodontic tooth movement (OTM) individually. Cementoblasts (OC/CM) located in the immediate vicinity of the fibroblasts on the cement have found way to the centre of actual research. Here, we identify and validate possible reference genes for OC/CM cells by RT-qPCR with and without static compressive loading.

Imaging and Analysis of Presynaptic Calcium Influx in Cultured Neurons Using synGCaMP6f.

Presynaptic Ca influx through voltage-gated calcium channels (VGCCs) is a key step in synaptic transmission that links action potential (AP)-derived depolarization to vesicle release. However, investigation of presynaptic Ca influx by patch clamp recordings is difficult due to the small size of the majority of synaptic boutons along thin axons that hamper clamp control. Genetically encoded calcium indicators (GECIs) in combination with live cell imaging provide an alternative method to study Ca transients in individual presynaptic terminals.

Molecular Dissection of Neurobeachin Function at Excitatory Synapses.

Spines are small protrusions from dendrites where most excitatory synapses reside. Changes in number, shape, and size of dendritic spines often reflect changes of neural activity in entire circuits or at individual synapses, making spines key structures of synaptic plasticity. Neurobeachin is a multidomain protein with roles in spine formation, postsynaptic neurotransmitter receptor targeting and actin distribution.

α-Neurexins Together with α2δ-1 Auxiliary Subunits Regulate Ca Influx through Ca2.1 Channels.

Action potential-evoked neurotransmitter release is impaired in knock-out neurons lacking synaptic cell-adhesion molecules α-neurexins (αNrxns), the extracellularly longer variants of the three vertebrate genes. Ca influx through presynaptic high-voltage gated calcium channels like the ubiquitous P/Q-type (Ca2.1) triggers release of fusion-ready vesicles at many boutons.

Immunogenicity testing of therapeutic antibodies in ocular fluids after intravitreal injection.

Aim: High drug concentrations in ocular fluids after intravitreal administration preclude the use of drug-sensitive immunoassays. A drug-tolerant immunoassay is therefore desirable for immunogenicity testing in ophthalmology.

Experimental: Immune complex (IC) antidrug antibody (ADA) assays were established for two species.

Do SSRIs and SNRIs reduce the frequency and/or severity of hot flashes in menopausal women.

Clinical Question: In menopausal women who experience regular hot flashes, does treatment with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) reduce the frequency and/or severity of hot flashes?

Answer: Yes. Review of the literature suggests that treatment with SSRIs or SNRIs reduces the frequency and severity of hot flashes in menopausal and post-menopausal women. Studies demonstrated that paroxetine (Paxil), citalopram (Celexa) and escitolapram (Lexapro) were the most effective SSRIs, and venlafaxine (Effexor) was the most effective first line SNRI, with desvenlafaxine as a second option.

Astrocyte pathology in a human neural stem cell model of frontotemporal dementia caused by mutant TAU protein.

Astroglial pathology is seen in various neurodegenerative diseases including frontotemporal dementia (FTD), which can be caused by mutations in the gene encoding the microtubule-associated protein TAU (MAPT). Here, we applied a stem cell model of FTD to examine if FTD astrocytes carry an intrinsic propensity to degeneration and to determine if they can induce non-cell-autonomous effects in neighboring neurons. We utilized CRISPR/Cas9 genome editing in human induced pluripotent stem (iPS) cell-derived neural progenitor cells (NPCs) to repair the FTD-associated N279K MAPT mutation.

Rapid and robust generation of long-term self-renewing human neural stem cells with the ability to generate mature astroglia.

Induced pluripotent stem cell bear the potential to differentiate into any desired cell type and hold large promise for disease-in-a-dish cell-modeling approaches. With the latest advances in the field of reprogramming technology, the generation of patient-specific cells has become a standard technology. However, directed and homogenous differentiation of human pluripotent stem cells into desired specific cell types remains an experimental challenge.

Deletion of KIBRA, protein expressed in kidney and brain, increases filopodial-like long dendritic spines in neocortical and hippocampal neurons in vivo and in vitro.

Spines are small protrusions arising from dendrites that receive most excitatory synaptic input in the brain. Dendritic spines represent dynamic structures that undergo activity-dependent adaptations, for example, during synaptic plasticity. Alterations of spine morphology, changes of spine type ratios or density have consequently been found in paradigms of learning and memory, and accompany many neuropsychiatric disorders.

Propofol for pediatric tracheal intubation with deep anesthesia during sevoflurane induction: dosing according to elapsed time for two age groups.

Study Objective: To determine, for two different age groups, the effect of duration of sevoflurane administration on the amount of propofol needed when performing tracheal intubation.

Design: Classic Dixon's Up-and-Down sequential method.

Setting: University based operating rooms.

Dendritic spine formation and synaptic function require neurobeachin.

A challenge in neuroscience is to understand the mechanisms underlying synapse formation. Most excitatory synapses in the brain are built on spines, which are actin-rich protrusions from dendrites. Spines are a major substrate of brain plasticity, and spine pathologies are observed in various mental illnesses.

Abnormalities in GABAergic synaptic transmission of intralaminar thalamic neurons in a genetic rat model of absence epilepsy.

Synaptic activity mediated via GABA receptors in thalamic circuits is critically involved in the generation of hypersynchrony associated with absence epilepsy. Neurons of "unspecific" intralaminar thalamic nuclei display characteristic burst patterns during seizure activity, although their synaptic properties remain largely unknown. Here, we used in vitro patch-clamp techniques in neurons of the paracentral (PC) thalamic nucleus, derived from a genetic model of absence epilepsy (WAG-Rij) and a non-epileptic control strain (ACI) to elucidate intrinsic and synaptic properties.

A key role for gp130 expressed on peripheral sensory nerves in pathological pain.

Interleukin-6 (IL-6) is a key mediator of inflammation. Inhibitors of IL-6 or of its signal transducing receptor gp130 constitute a novel class of anti-inflammatory drugs, which raise great hopes for improved treatments of painful inflammatory diseases such as rheumatoid arthritis. IL-6 and gp130 may enhance pain not only indirectly through their proinflammatory actions but also through a direct action on nociceptors (i.

Reversal of pathological pain through specific spinal GABAA receptor subtypes.

Inflammatory diseases and neuropathic insults are frequently accompanied by severe and debilitating pain, which can become chronic and often unresponsive to conventional analgesic treatment. A loss of synaptic inhibition in the spinal dorsal horn is considered to contribute significantly to this pain pathology. Facilitation of spinal gamma-aminobutyric acid (GABA)ergic neurotransmission through modulation of GABA(A) receptors should be able to compensate for this loss.

Modulation of synaptic activity in Purkinje neurons by ATP.

Adenosine triphosphate (ATP) is a versatile signalling molecule in the central and peripheral nervous system, where it can be released from both neurons and glial cells. In the cerebellum, ATP is released endogenously from the second postnatal week onwards, and is involved in the up-regulation of spontaneous synaptic input to Purkinje neurons by activation of purinergic P2 receptors. In the cerebellar cortex, ATP presumably acts on presynaptic inhibitory interneurons, which are excited by the activation of both P2X and P2Y receptors.

alpha1-Adrenergic modulation of synaptic input to Purkinje neurons in rat cerebellar brain slices.

The inhibitory activity in the cerebellar network, as investigated in acute brain slices from 14-20 days old rats, is modulated by alpha1-adrenergic stimulation. The specific alpha1-adrenoceptor agonist phenylephrine (PhE; 10 microM) or the alpha-adrenoceptor agonist 6-fluoronoradrenaline (10 microM) increases the frequency and the amplitude of spontaneous postsynaptic currents (sPSC) in Purkinje neurons. The effects are sensitive to the alpha1-adrenoceptor antagonists prazosin (30 microM) and phentolamine (10 microM).