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https://www.readbyqxmd.com/read/29234270/mouse-panx1-is-dispensable-for-hearing-acquisition-and-auditory-function
#1
Veronica Zorzi, Fabiola Paciello, Gaia Ziraldo, Chiara Peres, Flavia Mazzarda, Chiara Nardin, Miriam Pasquini, Francesco Chiani, Marcello Raspa, Ferdinando Scavizzi, Andrea Carrer, Giulia Crispino, Catalin D Ciubotaru, Hannah Monyer, Anna R Fetoni, Anna M Salvatore, Fabio Mammano
Panx1 forms plasma membrane channels in brain and several other organs, including the inner ear. Biophysical properties, activation mechanisms and modulators of Panx1 channels have been characterized in detail, however the impact of Panx1 on auditory function is unclear due to conflicts in published results. To address this issue, hearing performance and cochlear function of the Panx1-/- mouse strain, the first with a reported global ablation of Panx1, were scrutinized. Male and female homozygous (Panx1-/-), hemizygous (Panx1+/-) and their wild type (WT) siblings (Panx1+/+) were used for this study...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29232876/evaluation-of-fibrin-based-interpenetrating-polymer-networks-as-potential-biomaterials-for-tissue-engineering
#2
Olfat Gsib, Jean-Luc Duval, Mathieu Goczkowski, Marie Deneufchatel, Odile Fichet, Véronique Larreta-Garde, Sidi Ahmed Bencherif, Christophe Egles
Interpenetrating polymer networks (IPNs) have gained great attention for a number of biomedical applications due to their improved properties compared to individual components alone. In this study, we investigated the capacity of newly-developed naturally-derived IPNs as potential biomaterials for tissue engineering. These IPNs combine the biologic properties of a fibrous fibrin network polymerized at the nanoscale and the mechanical stability of polyethylene oxide (PEO). First, we assessed their cytotoxicity in vitro on L929 fibroblasts...
December 10, 2017: Nanomaterials
https://www.readbyqxmd.com/read/29226424/activation-of-ep2-receptor-suppresses-poly-i-c-and-lps-mediated-inflammation-in-primary-microglia-and-organotypic-hippocampal-slice-cultures-contributing-role-for-mapks
#3
Nizar M Yousif, Antonio Carlos Pinheiro de Oliveira, Simone Brioschi, Michael Huell, Knut Biber, Bernd L Fiebich
Brain inflammation is a critical factor involved in neurodegeneration. Recently, the prostaglandin E2 (PGE2 ) downstream members were suggested to modulate neuroinflammatory responses accompanying neurodegenerative diseases. In this study, we investigated the protective effects of prostaglandin E2 receptor 2 (EP2 ) during TLR3 and TLR4-driven inflammatory response using in vitro primary microglia and ex vivo organotypic hippocampal slice cultures (OHSCs). Depletion of microglia from OHSCs differentially affected TLR3 and TLR4 receptor expression...
December 11, 2017: Glia
https://www.readbyqxmd.com/read/29225566/cdk5-is-essential-for-amphetamine-to-increase-dendritic-spine-density-in-hippocampal-pyramidal-neurons
#4
Soledad Ferreras, Guillermo Fernández, Víctor Danelon, María V Pisano, Luján Masseroni, Christopher A Chapleau, Favio A Krapacher, Estela C Mlewski, Daniel H Mascó, Carlos Arias, Lucas Pozzo-Miller, María G Paglini
Psychostimulant drugs of abuse increase dendritic spine density in reward centers of the brain. However, little is known about their effects in the hippocampus, where activity-dependent changes in the density of dendritic spine are associated with learning and memory. Recent reports suggest that Cdk5 plays an important role in drug addiction, but its role in psychostimulant's effects on dendritic spines in hippocampus remain unknown. We used in vivo and in vitro approaches to demonstrate that amphetamine increases dendritic spine density in pyramidal neurons of the hippocampus...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29222792/preparation-of-rat-hippocampal-organotypic-cultures-and-application-to-study-amyloid-%C3%AE-peptide-toxicity
#5
Maria Rosanna Bronzuoli, Roberta Facchinetti, Caterina Scuderi
Hippocampal organotypic cultures constitute a very easy but delicate method widely used to study amyloid β-peptide toxicity. This ex vivo technique is performed on tissues isolated from newborn rats. Here, we describe a protocol for the preparation and culture of hippocampal organotypic slices that can be maintained for 14-21 days and their application to the study of amyloid β-peptide toxicity.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29221639/nerve-growth-factor-released-from-collagen-scaffolds-protects-axotomized-cholinergic-neurons-of-the-basal-nucleus-of-meynert-in-organotypic-brain-slices
#6
Bettina M Foidl, Buket Ucar, Alina Schwarz, Ana L Rebelo, Abhay Pandit, Christian Humpel
BACKGROUND: Alzheimeŕs disease is accompanied by cell death of cholinergic neurons, resulting in cognitive impairment and memory loss. Nerve growth factor (NGF) is the most potent protein to support survival of cholinergic neurons. New METHOD: Organotypic brain slices of the basal nucleus of Meynert (nBM) are a valuable tool to study cell death of axotomized cholinergic neurons, as well as protective effects of NGF added into the medium. The aim of the present study is to use collagen scaffolds crosslinked with polyethylineglycole and load with NGF to target delivery of NGF to organotypic nBM brain slices...
December 5, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29220201/engineering-hydrogel-microenvironments-to-recapitulate-the-stem-cell-niche
#7
Christopher M Madl, Sarah C Heilshorn
Stem cells are a powerful resource for many applications including regenerative medicine, patient-specific disease modeling, and toxicology screening. However, eliciting the desired behavior from stem cells, such as expansion in a naïve state or differentiation into a particular mature lineage, remains challenging. Drawing inspiration from the native stem cell niche, hydrogel platforms have been developed to regulate stem cell fate by controlling microenvironmental parameters including matrix mechanics, degradability, cell-adhesive ligand presentation, local microstructure, and cell-cell interactions...
December 8, 2017: Annual Review of Biomedical Engineering
https://www.readbyqxmd.com/read/29203823/three-dimensional-organotypic-matrices-from-alternative-collagen-sources-as-pre-clinical-models-for-cell-biology
#8
James R W Conway, Claire Vennin, Aurélie S Cazet, David Herrmann, Kendelle J Murphy, Sean C Warren, Lena Wullkopf, Alice Boulghourjian, Anaiis Zaratzian, Andrew M Da Silva, Marina Pajic, Jennifer P Morton, Thomas R Cox, Paul Timpson
Organotypic co-cultures bridge the gap between standard two-dimensional culture and mouse models. Such assays increase the fidelity of pre-clinical studies, to better inform lead compound development and address the increasing attrition rates of lead compounds within the pharmaceutical industry, which are often a result of screening in less faithful two-dimensional models. Using large-scale acid-extraction techniques, we demonstrate a step-by-step process to isolate collagen I from commercially available animal byproducts...
December 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29202785/anti-aggregant-tau-mutant-promotes-neurogenesis
#9
Maria Joseph, Marta Anglada-Huguet, Katharina Paesler, Eckhard Mandelkow, Eva-Maria Mandelkow
BACKGROUND: The microtubule-associated protein Tau plays a role in neurodegeneration as well as neurogenesis. Previous work has shown that the expression of the pro-aggregant mutant Tau repeat domain causes strong aggregation and pronounced neuronal loss in the hippocampus whereas the anti-aggregant form has no deleterious effects. These two proteins differ mainly in their propensity to form ß structure and hence to aggregate. METHODS: To elucidate the basis of these contrasting effects, we analyzed organotypic hippocampal slice cultures (OHSCs) from transgenic mice expressing the repeat domain (RD) of Tau with the anti-aggregant mutation (TauRDΔKPP) and compared them with slices containing pro-aggregant TauRDΔK...
December 4, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29196443/modelling-glioblastoma-tumour-host-cell-interactions-using-adult-brain-organotypic-slice-co-culture
#10
Maria Angeles Marques-Torrejon, Ester Gangoso, Steven M Pollard
Glioblastoma (GBM) is an aggressive incurable brain cancer. The cells that fuel the growth of tumours resemble neural stem cells found in the developing and adult mammalian forebrain. These are referred to as GBM stem cells (GSCs). Similar to neural stem cells, GSCs exhibit a variety of phenotypic states: dormant, quiescent, proliferative and differentiating. How environmental cues within the brain influence these distinct states is not well understood. Laboratory models of GBM can be generated using either genetically engineered mouse models, or via intracranial transplantation of cultured tumour initiating cells (mouse or human)...
December 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29192263/comprehensive-high-throughput-image-analysis-for-therapeutic-efficacy-of-architecturally-complex-heterotypic-organoids
#11
Anne-Laure Bulin, Mans Broekgaarden, Tayyaba Hasan
Bioengineered three-dimensional (3D) tumor models that incorporate heterotypic cellular communication are gaining interest as they can recapitulate key features regarding the intrinsic heterogeneity of cancer tissues. However, the architectural complexity and heterogeneous contents associated with these models pose a challenge for toxicological assays to accurately report treatment outcomes. To address this issue, we describe a comprehensive image analysis procedure for structurally complex organotypic cultures (CALYPSO) applied to fluorescence-based assays to extract multiparametric readouts of treatment effects for heterotypic tumor cultures that enables advanced analyses...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29176665/microbial-volatile-communication-in-human-organotypic-lung-models
#12
Layla J Barkal, Clare L Procknow, Yasmín R Álvarez-García, Mengyao Niu, José A Jiménez-Torres, Rebecca A Brockman-Schneider, James E Gern, Loren C Denlinger, Ashleigh B Theberge, Nancy P Keller, Erwin Berthier, David J Beebe
We inhale respiratory pathogens continuously, and the subsequent signaling events between host and microbe are complex, ultimately resulting in clearance of the microbe, stable colonization of the host, or active disease. Traditional in vitro methods are ill-equipped to study these critical events in the context of the lung microenvironment. Here we introduce a microscale organotypic model of the human bronchiole for studying pulmonary infection. By leveraging microscale techniques, the model is designed to approximate the structure of the human bronchiole, containing airway, vascular, and extracellular matrix compartments...
November 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29174800/ets1-induction-by-the-microenvironment-promotes-ovarian-cancer-metastasis-through-focal-adhesion-kinase
#13
Sunil Tomar, Joshua P Plotnik, James Haley, Joshua Scantland, Subramanyam Dasari, Zahir Sheikh, Robert Emerson, Dean Lenz, Peter C Hollenhorst, Anirban K Mitra
Metastatic colonization involves paracrine/juxtacrine interactions with the microenvironment inducing an adaptive response through transcriptional regulation. However, the identities of transcription factors (TFs) induced by the metastatic microenvironment in ovarian cancer (OC) and their mechanism of action is poorly understood. Using an organotypic 3D culture model recapitulating the early events of metastasis, we identified ETS1 as the most upregulated member of the ETS family of TFs in metastasizing OC cells as they interacted with the microenvironment...
November 21, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29172440/differential-behavior-of-the-mitochondrial-gsh-system-in-ca1-pyramidal-cells-and-astrocytes-during-oxygen-glucose-deprivation-and-reperfusion
#14
Bocheng Yin, German Barrionuevo, Stephen G Weber
Pyramidal cells and astrocytes have differential susceptibility to oxygen-glucose deprivation and reperfusion (OGD-RP). It is known that excessive reactive oxygen species (ROS) in mitochondria initiates the cell death, while glutathione (GSH) is one of the major defenses against ROS. Although it is known that astrocytes contain a higher concentration of GSH than neurons, and that astrocytes can provide neurons with GSH, we are unaware of a detailed and quantitative examination of the dynamic changes in the mitochondrial GSH system in the two cell types during OGD-RP...
November 27, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29170630/heterogeneity-of-the-axon-initial-segment-in-interneurons-and-pyramidal-cells-of-rodent-visual-cortex
#15
Felix Höfflin, Alexander Jack, Christian Riedel, Julia Mack-Bucher, Johannes Roos, Corinna Corcelli, Christian Schultz, Petra Wahle, Maren Engelhardt
The microdomain that orchestrates action potential initiation in neurons is the axon initial segment (AIS). It has long been considered to be a rather homogeneous domain at the very proximal axon hillock with relatively stable length, particularly in cortical pyramidal cells. However, studies in other brain regions paint a different picture. In hippocampal CA1, up to 50% of axons emerge from basal dendrites. Further, in about 30% of thick-tufted layer V pyramidal neurons in rat somatosensory cortex, axons have a dendritic origin...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29167235/cortisol-limits-selected-actions-of-synthetic-glucocorticoids-in-the-airway-epithelium
#16
Danica Prodanovic, Christine R Keenan, Shenna Langenbach, Meina Li, Qianyu Chen, Michael J Lew, Alastair G Stewart
Cortisol, a physiologic glucocorticoid (GC), is essential for growth and differentiation of the airway epithelium. Epithelial function influences inflammation in chronic respiratory diseases. Synthetic GCs, including inhaled corticosteroids, exert anti-inflammatory effects in airway epithelium by transactivation of genes and by inhibition of proinflammatory cytokine release. We examined the effect of cortisol on the actions of synthetic GCs in the airway epithelium, demonstrating that cortisol acts like a partial agonist at the GC receptor (GR), limiting GC-induced GR-dependent transcription in the BEAS-2B human bronchial epithelial cell line...
November 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29165315/an-expression-screen-for-aged-dependent-micrornas-identifies-mir-30a-as-a-key-regulator-of-aging-features-in-human-epidermis
#17
Charlotte Muther, Lara Jobeili, Maëlle Garion, Sandrine Heraud, Amélie Thepot, Odile Damour, Jérôme Lamartine
The mechanisms affecting epidermal homeostasis during aging remain poorly understood. To identify age-related microRNAs, a class of non-coding RNAs known to play a key role in the regulation of epidermal homeostasis, an exhaustive miRNA expression screen was performed in human keratinocytes from young or elderly subjects. Many microRNAs modulated by aging were identified, including miR-30a, in which both strands were overexpressed in aged cells and epidermal tissue. Stable MiR-30a over-expression strongly impaired epidermal differentiation, inducing severe barrier function defects in an organotypic culture model...
November 19, 2017: Aging
https://www.readbyqxmd.com/read/29160116/assessment-of-aav-serotype-tropism-in-human-retinal-explants
#18
Luke Aaron Wiley, Erin Burnight, Emily E Kaalberg, Chunhua Jiao, Megan J Riker, Jennifer A Halder, Meagan A Luse, Ian C Han, Stephen R Russell, Elliott H Sohn, Edwin Stone, Budd A Tucker, Robert F Mullins
Advances in the discovery of the causes of monogenic retinal disorders, combined with technologies for the delivery of DNA to the retina, offer enormous opportunities for the treatment of previously untreatable blinding diseases. However, for gene augmentation to be most effective, vectors that have the correct cell-type specificity are needed. While animal models are very useful, they often exhibit differences in retinal cell surface receptors compared to human retina. In this study, we evaluated the use of an ex vivo organotypic explant system to test the transduction efficiency and tropism of 7 different adeno-associated viral type 2 (AAV2) serotypes in human retina and retinal pigment epithelium-choroid: AAV2/1, AAV2/2, AAV2/4, AAV2/5, AAV2/6, AAV2/8, and AAV2/9, all driving expression of GFP under control of the cytomegalovirus promoter...
November 21, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29143997/epidermal-neural-crest-stem-cell-derived-glia-enhance-neurotrophic-elements-in-an-ex-vivo-model-of-spinal-cord-injury
#19
Sareh Pandamooz, Mohammad Saied Salehi, Mohammad Ismail Zibaii, Abolhassan Ahmadiani, Mohammad Nabiuni, Leila Dargahi
Growing evidence that cell-based therapies can improve recovery outcome in spinal cord injury (SCI) models substantiates their application for treatment of human with SCI. To address the effectiveness of these stem cells, potential candidates should be evaluated in proper SCI platform that allows direct real-time monitoring. In this study, the role of epidermal neural crest stem cells (EPI-NCSCs) was elucidated in an ex vivo model of SCI and valproic acid (VPA) was administered to ameliorate the inhospitable context of injury for grafted EPI-NCSCs...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29138531/anti-inflammatory-strategy-for-m2-microglial-polarization-using-retinoic-acid-loaded-nanoparticles
#20
Marta Machado-Pereira, Tiago Santos, Lino Ferreira, Liliana Bernardino, Raquel Ferreira
Inflammatory mechanisms triggered by microglial cells are involved in the pathophysiology of several brain disorders, hindering repair. Herein, we propose the use of retinoic acid-loaded polymeric nanoparticles (RA-NP) as a means to modulate microglia response towards an anti-inflammatory and neuroprotective phenotype (M2). RA-NP were first confirmed to be internalized by N9 microglial cells; nanoparticles did not affect cell survival at concentrations below 100 μg/mL. Then, immunocytochemical studies were performed to assess the expression of pro- and anti-inflammatory mediators...
2017: Mediators of Inflammation
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