361 research outputs found

    Na+/Ca2+ exchanger isoform 1 takes part to the Ca2+-related prosurvival pathway of SOD1 in primary motor neurons exposed to beta-methylamino-l-alanine

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    Background: The cycad neurotoxin beta-methylamino-l-alanine (L-BMAA), one of the environmental trigger factor for amyotrophic lateral sclerosis/Parkinson-dementia complex (ALS/PDC), may cause neurodegeneration by disrupting organellar Ca2+ homeostasis. Through the activation of Akt/ERK1/2 pathway, the Cu,Zn-superoxide dismutase (SOD1) and its non-metallated form, ApoSOD1, prevent endoplasmic reticulum (ER) stress-induced cell death in motor neurons exposed to L-BMAA. This occurs through the rapid increase of intracellular Ca2+ concentration ([Ca2+]i) in part flowing from the extracellular compartment and in part released from ER. However, the molecular components of this mechanism remain uncharacterized. Methods: By an integrated approach consisting on the use of siRNA strategy, Western blotting, confocal double- labeling immunofluorescence, patch-clamp electrophysiology, and Fura 2-/SBFI-single-cell imaging, we explored in rat motor neuron-enriched cultures the involvement of the plasma membrane proteins Na+/Ca2+ exchanger (NCX) and purinergic P2X7 receptor as well as that of the intracellular cADP-ribose (cADPR) pathway, in the neuroprotective mechanism of SOD1. Results: We showed that SOD1-induced [Ca2+]i rise was prevented neither by A430879, a P2X7 receptor specific antagonist or 8-bromo-cADPR, a cell permeant antagonist of cADP-ribose, but only by the pan inhibitor of NCX, CB-DMB. The same occurred for the ApoSOD1. Confocal double labeling immunofluorescence showed a huge expression of plasmalemmal NCX1 and intracellular NCX3 isoforms. Furthermore, we identified NCX1 reverse mode as the main mechanism responsible for the neuroprotective ER Ca2+ refilling elicited by SOD1 and ApoSOD1 through which they promoted translocation of active Akt in the nuclei of a subset of primary motor neurons. Finally, the activation of NCX1 by the specific agonist CN-PYB2 protected motor neurons from L-BMAA-induced cell death, mimicking the effect of SOD1. Conclusion: Collectively, our data indicate that SOD1 and ApoSOD1 exert their neuroprotective effect by modulating ER Ca2+ content through the activation of NCX1 reverse mode and Akt nuclear translocation in a subset of primary motor neurons. [MediaObject not available: see fulltext.

    The impact of COVID-19 on radiological findings in patients accessing the emergency department: a multicentric study

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    The aim of this multicentric study is to illustrate how the COVID-19 pandemic lockdown affected the workload and outcomes of radiological examinations in emergency radiology

    On the Shear Instability in Relativistic Neutron Stars

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    We present new results on instabilities in rapidly and differentially rotating neutron stars. We model the stars in full general relativity and describe the stellar matter adopting a cold realistic equation of state based on the unified SLy prescription. We provide evidence that rapidly and differentially rotating stars that are below the expected threshold for the dynamical bar-mode instability, beta_c = T/|W| ~ 0.25, do nevertheless develop a shear instability on a dynamical timescale and for a wide range of values of beta. This class of instability, which has so far been found only for small values of beta and with very small growth rates, is therefore more generic than previously found and potentially more effective in producing strong sources of gravitational waves. Overall, our findings support the phenomenological predictions made by Watts, Andersson and Jones on the nature of the low-T/|W|.Comment: 20 pages; accepted to the Classical and Quantum Gravity special issue for MICRA200
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