Search results for "46"
showing 10 items of 1176 documents
An Assay to Determine Mechanisms of Rapid Autoantibody-Induced Neurotransmitter Receptor Endocytosis and Vesicular Trafficking in Autoimmune Encephal…
2019
N-Methyl-D-aspartate (NMDA) receptors (NMDARs) are among the most important excitatory neurotransmitter receptors in the human brain. Autoantibodies to the human NMDAR cause the most frequent form of autoimmune encephalitis involving autoantibody-mediated receptor cross-linking and subsequent internalization of the antibody-receptor complex. This has been deemed to represent the predominant antibody effector mechanism depleting the NMDAR from the synaptic and extra-synaptic neuronal cell membrane. To assess in detail the molecular mechanisms of autoantibody-induced NMDAR endocytosis, vesicular trafficking, and exocytosis we transiently co-expressed rat GluN1-1a-EGFP and GluN2B-ECFP alone or…
Coexpresión de NG2/GFAP tras la diferenciación en células transfectadas con las mutaciones de GFAP y en células procedentes de gliomas indiferenciados
2020
Resumen: Introducción: La enfermedad de Alexander es una enfermedad rara causada por mutaciones en el gen que codifica la proteína glial ácida fibrilar (GFAP). En un estudio previo hemos observado que la diferenciación de neuroesferas transfectadas con estas mutaciones genera un tipo celular que comparte la expresión de GFAP y NG2. Objetivos: Determinar el efecto de las mutaciones en marcadores moleculares en comparación con células de glioma diferenciados que expresan simultáneamente GFAP y NG2. Métodos: Se utilizaron muestras de glioblastoma humana (GLM) y neuroesferas procedentes de rata transfectadas con mutaciones de GFAP para el análisis de la expresión tras diferenciación de GFAP y N…
Expression of endogenous mouse APP modulates β-amyloid deposition in hAPP-transgenic mice
2017
Amyloid-β (Aβ) deposition is one of the hallmarks of the amyloid hypothesis in Alzheimer’s disease (AD). Mouse models using APP-transgene overexpression to generate amyloid plaques have shown to model only certain parts of the disease. The extent to which the data from mice can be transferred to man remains controversial. Several studies have shown convincing treatment results in reducing Aβ and enhancing cognition in mice but failed totally in human. One model-dependent factor has so far been almost completely neglected: the endogenous expression of mouse APP and its effects on the transgenic models and the readout for therapeutic approaches. Here, we report that hAPP-transgenic models of …
Magnetic Nanoparticle-Based Hyperthermia Mediates Drug Delivery and Impairs the Tumorigenic Capacity of Quiescent Colorectal Cancer Stem Cells
2021
Cancer stem cells (CSCs) are the tumor cell subpopulation responsible for resistance to chemotherapy, tumor recurrence, and metastasis. An efficient therapy must act on low proliferating quiescent-CSCs (q-CSCs). We here investigate the effect of magnetic hyperthermia (MHT) in combination with local chemotherapy as a dual therapy to inhibit patient-derived colorectal qCR-CSCs. We apply iron oxide nanocubes as MHT heat mediators, coated with a thermoresponsive polymer (TR-Cubes) and loaded with DOXO (TR-DOXO) as a chemotherapeutic agent. The thermoresponsive polymer releases DOXO only at a temperature above 44 °C. In colony-forming assays, the cells exposed to TR-Cubes with MHT reveal that qC…
TLR4 participates in the transmission of ethanol-induced neuroinflammation via astrocyte-derived extracellular vesicles
2019
Background Current evidence indicates that extracellular vesicles (EVs) participate in intercellular signaling, and in the regulation and amplification of neuroinflammation. We have previously shown that ethanol activates glial cells through Toll-like receptor 4 (TLR4) by triggering neuroinflammation. Here, we evaluate if ethanol and the TLR4 response change the release and inflammatory content of astrocyte-derived EVs, and whether these vesicles are capable of communicating with neurons by spreading neuroinflammation. Methods Cortical neurons and astrocytes in culture were used. EVs were isolated from the extracellular medium of the primary culture of the WT and TLR4-KO astrocytes treated …
Deep Brain Stimulation and L-DOPA Therapy: Concepts of Action and Clinical Applications in Parkinson's Disease.
2018
L-DOPA is still the most effective pharmacological therapy for the treatment of motor symptoms in Parkinson's disease (PD) almost four decades after it was first used. Deep brain stimulation (DBS) is a safe and highly effective treatment option in patients with PD. Even though a clear understanding of the mechanisms of both treatment methods is yet to be obtained, the combination of both treatments is the most effective standard evidenced-based therapy to date. Recent studies have demonstrated that DBS is a therapy option even in the early course of the disease, when first complications arise despite a rigorous adjustment of the pharmacological treatment. The unique feature of this therapeu…
Virgin olive oil enriched with its own phenolic compounds or complemented with thyme improves endothelial function: The potential role of plasmatic f…
2017
The aim of the present study was to assess whether different functional virgin olive oils (FVOOs) with varying phenolic compounds (PC) could protect the plasmatic fat-soluble vitamins, which in turn could improve the endothelial function. In order to select the optimal phenolic dose in the improvement of ischemic reactive hyperemia (IRH), a dose-response study (n = 12, healthy subjects) was performed and the enrichment of 500 mg PC/kg oil was selected. In a 3-week cross-over sustained study (n = 33 hypercholesterolemic subjects), the consumption of 25 mL/day of two phenol-enriched olive oils (one enriched with its own PC and another combined with thyme PC) increased IRH and plasma concentra…
Amyotrophic lateral sclerosis modifies progenitor neural proliferation in adult classic neurogenic brain niches.
2017
Background Adult neurogenesis persists through life at least in classic neurogenic niches. Neurogenesis has been previously described as reduced in neurodegenerative diseases. There is not much knowledge about is adult neurogenesis is or not modified in amyotrophy lateral sclerosis (ALS). All previous publications has studied the ALS SOD1 (superoxide dismutase) transgenic mouse model. The purpose of this study is to examine the process of adult neurogenesis in classic niches (subventricular zone [SVZ] and subgranular zone [SGZ] of the dentate gyrus) in patients with amyotrophic lateral sclerosis (ALS), both with (ALS-FTD) and without associated frontotemporal dementia (FTD). Methods We stud…
Software-based analysis of 1-hour Holter ECG to select for prolonged ECG monitoring after stroke.
2020
Abstract Objective Identification of ischemic stroke patients at high risk for paroxysmal atrial fibrillation (pAF) during 72 hours Holter ECG might be useful to individualize the allocation of prolonged ECG monitoring times, currently not routinely applied in clinical practice. Methods In a prospective multicenter study, the first analysable hour of raw ECG data from prolonged 72 hours Holter ECG monitoring in 1031 patients with acute ischemic stroke/TIA presenting in sinus rhythm was classified by an automated software (AA) into “no risk of AF” or “risk of AF” and compared to clinical variables to predict AF during 72 hours Holter‐ECG. Results pAF was diagnosed in 54 patients (5.2%; mean …
Myelin changes in Alexander disease
2018
Introduction: Alexander disease (AxD) is a type of leukodystrophy. Its pathological basis, along with myelin loss, is the appearance of Rosenthal bodies, which are cytoplasmic inclusions in astrocytes. Mutations in the gene coding for glial fibrillary acidic protein (GFAP) have been identified as a genetic basis for AxD. However, the mechanism by which these variants produce the disease is not understood. Development: The most widespread hypothesis is that AxD develops when a gain-of-function mutation causes an increase in GFAP. However, this mechanism does not explain myelin loss, given that experimental models in which GFAP expression is normal or mutated do not exhibit myelin disorders. …