Search results for "OTR"

2021

Brain homeostasis is the dynamic equilibrium whereby physiological parameters are kept actively within a specific range. The homeostatic range is not fixed and may change throughout the individual's lifespan, or may be transiently modified in the presence of severe perturbations. The endocannabinoid system has emerged as a safeguard of homeostasis, e.g., it modulates neurotransmission and protects neurons from prolonged or excessively strong activation. We used genetically engineered mouse lines that lack the cannabinoid type-1 receptor (CB1) either in dorsal telencephalic glutamatergic or in forebrain GABAergic neurons to create new allostatic states, resulting from alterations in the exci…

Localization of the cannabinoid type-1 receptor in subcellular astrocyte compartments of mutant mouse hippocampus

2018

Astroglial type‐1 cannabinoid (CB1) receptors are involved in synaptic transmission, plasticity and behavior by interfering with the so‐called tripartite synapse formed by pre‐ and post‐synaptic neuronal elements and surrounding astrocyte processes. However, little is known concerning the subcellular distribution of astroglial CB1 receptors. In particular, brain CB1 receptors are mostly localized at cells' plasmalemma, but recent evidence indicates their functional presence in mitochondrial membranes. Whether CB1 receptors are present in astroglial mitochondria has remained unknown. To investigate this issue, we included conditional knock‐out mice lacking astroglial CB1 receptor expression …

Determination of meropenem in endotracheal tubes by in-tube solid phase microextraction coupled to capillary liquid chromatography with diode array d…

2017

Meropenem is a widely used antimicrobial for the treatment of infections associated with the use of invasive medical devices in intensive care unit patients. These treatments are not always effective, in fact, in-vitro studies have demonstrated the difficulty of antimicrobials to penetrate into the biofilm, however in-vivo studies of the effect of these compounds is a trend, mostly because of the complexity of pulmonary samples extracted from ETTs. Therefore, the objective of this study was to evaluate in-tube solid phase microextraction (in-tube SPME) coupled to capillary liquid chromatography (CapLC) with DAD to determine meropenem in Errs in order to estimate the penetration capability i…

Autism Related Neuroligin-4 Knockout Impairs Intracortical Processing but not Sensory Inputs in Mouse Barrel Cortex

2016

Neuroligin-4 (Nlgn4) is a cell adhesion protein that regulates synapse organization and function. Mutations in human NLGN4 are among the causes of autism spectrum disorders. In mouse, Nlgn4 knockout (KO) perturbs GABAergic synaptic transmission and oscillatory activity in hippocampus, and causes social interaction deficits. The complex profile of cellular and circuit changes that are caused by Nlgn4-KO is still only partly understood. Using Nlgn4-KO mice, we found that Nlgn4-KO increases the power in the alpha frequency band of spontaneous network activity in the barrel cortex under urethane anesthesia in vivo. Nlgn4-KO did not affect single-whisker-induced local field potentials, but suppr…

Comparative study of eco- and cytotoxicity during biotransformation of anthraquinone dye Alizarin Blue Black B in optimized cultures of microscopic f…

2017

The aim of this study was to select optimal conditions (C and N sources, initial pH and temperature) for biodecolorization of 0.03% anthraquinone dye Alizarin Blue Black B (ABBB) by microscopic fungi: Haematonectria haematococca BwIII43, K37 and Trichoderma harzianum BsIII33. The phenolic compounds, phytotoxicity (Lepidium sativum L.), biotoxicity (Microtox), cytotoxicity and yeast viability assay were performed to determine the extent of ABBB detoxification. Biodecolorization and detoxification of 0.03% ABBB in H. haematococca BwIII43 and T. harzianum BsIII33 cultures was correlated with extracellular oxidoreductases activity. In turn, secondary products, toxic to human fibroblasts and res…

Albumin-Folate Conjugates for Drug-targeting in Photodynamic Therapy.

2016

Photodynamic therapy (PDT) is based on the cytotoxicity of photosensitizers in the presence of light. Increased selectivity and effectivity of the treatment is expected if a specific uptake of the photosensitizers into the target cells, often tumor cells, can be achieved. An attractive transporter for that purpose is the folic acid receptor α (FRα), which is overexpressed on the surface of many tumor cells and mediates an endocytotic uptake. Here, we describe the synthesis and photobiological characterization of polar β-carboline derivatives as photosensitizers covalently linked to folate-tagged albumin as the carrier system. The particles were taken up by KB (human carcinoma) cells within …

Microtubule disruption changes endothelial cell mechanics and adhesion

2019

AbstractThe interest in studying the mechanical and adhesive properties of cells has increased in recent years. The cytoskeleton is known to play a key role in cell mechanics. However, the role of the microtubules in shaping cell mechanics is not yet well understood. We have employed Atomic Force Microscopy (AFM) together with confocal fluorescence microscopy to determine the role of microtubules in cytomechanics of Human Umbilical Vein Endothelial Cells (HUVECs). Additionally, the time variation of the adhesion between tip and cell surface was studied. The disruption of microtubules by exposing the cells to two colchicine concentrations was monitored as a function of time. Already, after 3…

A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem ce…

2016

AbstractHutchinson-Gilford progeria syndrome (HGPS) is a rare fatal genetic disorder that causes systemic accelerated aging in children. Thanks to the pluripotency and self-renewal properties of induced pluripotent stem cells (iPSC), HGPS iPSC-based modeling opens up the possibility of access to different relevant cell types for pharmacological approaches. In this study, 2800 small molecules were explored using high-throughput screening, looking for compounds that could potentially reduce the alkaline phosphatase activity of HGPS mesenchymal stem cells (MSCs) committed into osteogenic differentiation. Results revealed seven compounds that normalized the osteogenic differentiation process an…

Bifidobacterium CECT 7765 modulates early stress-induced immune, neuroendocrine and behavioral alterations in mice.

2016

Emerging evidence suggests that there is a window of opportunity within the early developmental period, when microbiota-based interventions could play a major role in modulating the gut-brain axis and, thereby, in preventing mood disorders. This study aims at evaluating the effects and mode of action of Bifidobacterium pseudocatenulatum CECT 7765 in a murine model of chronic stress induced by maternal separation (MS). C57Bl/6J male breast-fed pups were divided into four groups, which were subjected or not to MS and supplemented with placebo or B. pseudocatenulatum CECT7765 until postnatal period (P) 21 and followed-up until P41. Behavioral tests were performed and neuroendocrine parameters …

Opposing Effects of CREBBP Mutations Govern the Phenotype of Rubinstein-Taybi Syndrome and Adult SHH Medulloblastoma

2018

Recurrent mutations in chromatin modifiers are specifically prevalent in adolescent or adult patients with Sonic hedgehog-associated medulloblastoma (SHH MB). Here, we report that mutations in the acetyltransferase CREBBP have opposing effects during the development of the cerebellum, the primary site of origin of SHH MB. Our data reveal that loss of Crebbp in cerebellar granule neuron progenitors (GNPs) during embryonic development of mice compromises GNP development, in part by downregulation of brain-derived neurotrophic factor (Bdnf). Interestingly, concomitant cerebellar hypoplasia was also observed in patients with Rubinstein-Taybi syndrome, a congenital disorder caused by germline mu…