Morphological Differentiation Towards Neuronal Phenotype of SH-SY5Y Neuroblastoma Cells by Estradiol, Retinoic Acid and Cholesterol

Human SH-SY5Y neuroblastoma cells maintain their potential for differentiation and regression in culture conditions. The induction of differentiation could serve as a strategy to inhibit cell proliferation and tumor growth. Previous studies have shown that differentiation of SH-SY5Y cells can be induced by all-trans-retinoic-acid (RA) and cholesterol (CHOL). However, signaling pathways that lead to terminal differentiation of SH-SY5Y cells are still largely unknown. The goal of this study was to examine in the RA and CHOL treated SH-SY5Y cells the additive impacts of estradiol (E2) and brain-derived neurotrophic factor (BDNF) on cell morphology, cell population growth, synaptic vesicle recycling and presence of neurofilaments. The above features indicate a higher level of neuronal differentiation. Our data show that treatment for 10 days in vitro (DIV) with RA alone or when combined with E2 (RE) or CHOL (RC), but not when combined with BDNF (RB), significantly (p < 0.01) inhibited the cell population growth. Synaptic vesicle recycling, induced by high-K+ depolarization, was significantly increased in all treatments where RA was included (RE, RC, RB, RCB), and when all agents were added together (RCBE). Specifically, our results show for the first time that E2 treatment can alone increase synaptic vesicle recycling in SH-SY5Y cells. This work contributes to the understanding of the ways to improve suppression of neuroblastoma cells’ population growth by inducing maturation and differentiation

Effects of Transmitters and Amyloid-Beta Peptide on Calcium Signals in Rat Cortical Astrocytes: Fura-2AM Measurements and Stochastic Model Simulations

BACKGROUND: To better understand the complex molecular level interactions seen in the pathogenesis of Alzheimer's disease, the results of the wet-lab and clinical studies can be complemented by mathematical models. Astrocytes are known to become reactive in Alzheimer's disease and their ionic equilibrium can be disturbed by interaction of the released and accumulated transmitters, such as serotonin, and peptides, including amyloid- peptides (A). We have here studied the effects of small amounts of A25-35 fragments on the transmitter-induced calcium signals in astrocytes by Fura-2AM fluorescence measurements and running simulations of the detected calcium signals. METHODOLOGY/PRINCIPAL FINDINGS: Intracellular calcium signals were measured in cultured rat cortical astrocytes following additions of serotonin and glutamate, or either of these transmitters together with A25-35. A25-35 increased the number of astrocytes responding to glutamate and exceedingly increased the magnitude of the serotonin-induced calcium signals. In addition to A25-35-induced effects, the contribution of intracellular calcium stores to calcium signaling was tested. When using higher stimulus frequency, the subsequent calcium peaks after the initial peak were of lower amplitude. This may indicate inadequate filling of the intracellular calcium stores between the stimuli. In order to reproduce the experimental findings, a stochastic computational model was introduced. The model takes into account the major mechanisms known to be involved in calcium signaling in astrocytes. Model simulations confirm the principal experimental findings and show the variability typical for experimental measurements. CONCLUSIONS/SIGNIFICANCE: Nanomolar A25-35 alone does not cause persistent change in the basal level of calcium in astrocytes. However, even small amounts of A25-35, together with transmitters, can have substantial synergistic effects on intracellular calcium signals. Computational modeling further helps in understanding the mechanisms associated with intracellular calcium oscillations. Modeling the mechanisms is important, as astrocytes have an essential role in regulating the neuronal microenvironment of the central nervous system

Signaaleista tulevaisuustarinoihin : ennakoinnin lyhyt käsikirja

Kukaan ei tiedä, mitä tulevaisuudessa tapahtuu. Tulevaisuus sisältää yllätyksiä, mutta myös niihin voi valmistautua. Ennakoinnin lyhyessä käsikirjassa esitellään ajattelu- ja toimintatapoja, joita soveltamalla kuka tahansa voi valmistautua tulevaisuuden kohtaamiseen. Käsittelemme tulevaisuuteen liittyviä tiedollisia haasteita ja niiden kohtaamisen tapoja. Käsikirjamme ydin rakentuu ennakointiprosessille, joka jakautuu kolmeen vaiheeseen ’Sensing’ (luotaaminen), ’Sensemaking’ (merkityksellistäminen) ja ’Seizing’ (haltuunotto). Ennakoinnin lyhyen käsikirjan tavoitteena ei ole tarjota kaiken kattavaa yhteenvetoa erilaisista ennakointimenetelmistä, sillä kuvaamme ennakointiajattelun soveltamista sosiaalisen investoinnin kontekstissa. Käsikirja on osa Horizon 2020-ohjelmasta rahoitettua InnoSI-hanketta

From signals to future stories : a handbook for applying foresight in the field of welfare

We don’t know what will happen in coming years. The future is always unknown, however, we cannot just sit and wait what will happen. The future may surprise but our changes to survive depends on our preparedness. To tackle the unknowns of the future in the field of welfare, this handbook emphasises foresightfulness instead of future thinking techniques. The handbook introduces the foresight flow consisting of three phases: sensing, sensemaking and seizing. The handbook is not written to explore what may happen, but how the future can be thought. It is believed that the more convincingly the future is told, the more it guides today’s decisions