Search results for " Plastic"
showing 10 items of 3463 documents
Physiological Functions of the β-Site Amyloid Precursor Protein Cleaving Enzyme 1 and 2
2017
BACE1 was discovered as the β-secretase for initiating the cleavage of amyloid precursor protein (APP) at the β-secretase site, while its close homology BACE2 cleaves APP within the β-amyloid (Aβ) domain region and shows distinct cleavage preferences in vivo. Inhibition of BACE1 proteolytic activity has been confirmed to decrease Aβ generation and amyloid deposition, and thus specific inhibition of BACE1 by small molecules is a current focus for Alzheimer’s disease therapy. While BACE1 inhibitors are being tested in advanced clinical trials, knowledge regarding the properties and physiological functions of BACE is highly important and this review summarizes advancements in BACE1 research ov…
Characterization and isolation of immature neurons of the adult mouse piriform cortex
2015
Physiological studies indicate that the piriform or primary olfactory cortex of adult mammals exhibits a high degree of synaptic plasticity. Interestingly, a subpopulation of cells in the layer II of the adult piriform cortex expresses neurodevelopmental markers, such as the polysialylated form of neural cell adhesion molecule (PSA-NCAM) or doublecortin (DCX). This study analyzes the nature, origin, and potential function of these poorly understood cells in mice. As previously described in rats, most of the PSA-NCAM expressing cells in layer II could be morphologically classified as tangled cells and only a small proportion of larger cells could be considered semilunar-pyramidal transitiona…
Dynamic compartmentalization of calcium channel signalling in neurons.
2020
Calcium fluxes through the neuronal membrane are strictly limited in time due to biophysical properties of voltage-gated and ligand-activated ion channels and receptors. Being embedded into the crowded dynamic environment of biological membranes, Ca2+-permeable receptors and channels undergo perpetual spatial rearrangement, which enables their temporary association and formation of transient signalling complexes. Thus, efficient calcium-mediated signal transduction requires mechanisms to support very precise spatiotemporal alignment of the calcium source and Ca2+-binding lipids and proteins in a highly dynamic environment. The mobility of calcium channels and calcium-sensing proteins themse…
Are There Knots in Chromosomes?
2017
Recent developments have for the first time allowed the determination of three-dimensional structures of individual chromosomes and genomes in nuclei of single haploid mouse embryonic stem (ES) cells based on Hi⁻C chromosome conformation contact data. Although these first structures have a relatively low resolution, they provide the first experimental data that can be used to study chromosome and intact genome folding. Here we further analyze these structures and provide the first evidence that G1 phase chromosomes are knotted, consistent with the fact that plots of contact probability vs sequence separation show a power law dependence that is intermediate between that of a fractal globule …
Enhancement of Wound Healing in Normal and Diabetic Mice by Topical Application of Amorphous Polyphosphate. Superior Effect of a Host⁻Guest Composite…
2017
The effect of polyphosphate (polyP) microparticles on wound healing was tested both in vitro and in a mice model in vivo. Two approaches were used: pure salts of polyphosphate, fabricated as amorphous microparticles (MPs, consisting of calcium and magnesium salts of polyP, “Ca–polyp-MPs” and “Mg–polyp-MPs”), and host–guest composite particles, prepared from amorphous collagen (host) and polyphosphate (guest), termed “col/polyp-MPs”. Animal experiments with polyP on healing of excisional wounds were performed using both normal mice and diabetic mice. After a healing period of 7 days “Ca–polyp-MP” significantly improved re-epithelialization in normal mice from 31% (control) to 72% (polyP micr…
Coincident Activation of Glutamate Receptors Enhances GABAA Receptor-Induced Ionic Plasticity of the Intracellular Cl−-Concentration in Dissociated N…
2019
Massive activation of γ-amino butyric acid A (GABAA) receptors during pathophysiological activity induces an increase in the intracellular Cl−-concentration ([Cl−]i), which is sufficient to render GABAergic responses excitatory. However, to what extent physiological levels of GABAergic activity can influence [Cl−]i is not known. Aim of the present study is to reveal whether moderate activation of GABAA receptors mediates functionally relevant [Cl−]i changes and whether these changes can be augmented by coincident glutamatergic activity. To address these questions, we used whole-cell patch-clamp recordings from cultured cortical neurons [at days in vitro (DIV) 6–22] to determine changes in t…
The stressed cytoskeleton: How actin dynamics can shape stress-related consequences on synaptic plasticity and complex behavior
2015
Stress alters synaptic plasticity but the molecular and cellular mechanisms through which environmental stimuli modulate synaptic function remain to be elucidated. Actin filaments are the major structural component of synapses and their rearrangements by actin-binding proteins (ABPs) are critical for fine-tuning synaptic plasticity. Accumulating evidence suggests that some ABPs are specifically regulated by stress and stress-related effectors such as glucocorticoids and corticotropin releasing hormone. ABPs may thus be central in stress-induced perturbations at the level of synaptic plasticity, leading to impairments in behavioral domains including cognitive performance and social behavior.…
Effects of PSA Removal from NCAM on the Critical Period Plasticity Triggered by the Antidepressant Fluoxetine in the Visual Cortex.
2016
Neuronal plasticity peaks during critical periods of postnatal development and is reduced towards adulthood. Recent data suggests that windows of juvenile-like plasticity can be triggered in the adult brain by antidepressant drugs such as Fluoxetine. Although the exact mechanisms of how Fluoxetine promotes such plasticity remains unknown, several studies indicate that inhibitory circuits play an important role. The polysialylated form of the neural cell adhesion molecules (PSA-NCAM) has been suggested to mediate the effects of Fluoxetine and it is expressed in the adult brain by mature interneurons. Moreover, the enzymatic removal of PSA by neuroaminidase-N not only affects the structure of…
Mechanisms Underlying Memory Consolidation by Adult-Born Neurons During Sleep
2020
The mammalian hippocampus generates new neurons that incorporate into existing neuronal networks throughout the lifespan, which bestows a unique form of cellular plasticity to the memory system. Recently, we found that hippocampal adult-born neurons (ABNs) that were active during learning reactivate during subsequent rapid eye movement (REM) sleep and provided causal evidence that ABN activity during REM sleep is necessary for memory consolidation. Here, we describe the potential underlying mechanisms by highlighting distinct characteristics of ABNs including decoupled firing from local oscillations and ability to undergo profound synaptic remodeling in response to experience. We further di…
Exosome-Mediated Signaling in Epithelial to Mesenchymal Transition and Tumor Progression
2018
Growing evidence points to exosomes as key mediators of cell–cell communication, by transferring their specific cargo (e.g., proteins, lipids, DNA and RNA molecules) from producing to receiving cells. In cancer, the regulation of the exosome-mediated intercellular communication may be reshaped, inducing relevant changes in gene expression of recipient cells in addition to microenvironment alterations. Notably, exosomes may deliver signals able to induce the transdifferentiation process known as Epithelial-to-Mesenchymal Transition (EMT). In this review, we summarize recent findings on the role of exosomes in tumor progression and EMT, highlighting current knowledge on exosome-mediated inter…