No TNF-α, IL-1β or IL-10 was detected in the cochlear perilymph after the loss of most auditory hair cells, indicating the absence of severe inflammation. In contrast, Selleckchem Autophagy inhibitor we observed a significant and temporary increase in the level of extracellular high mobility group box 1 (HMGB1), a late mediator of inflammation that also functions as a signal of tissue damage. This increase coincided with epithelial remodelling of the injured organ of Corti, and occurred concomitantly with robust and transient cytoplasmic expression of acetylated HMGB1 within the non-sensory supporting cells,
Deiters cells. Here, HMGB1 was found to be enclosed within vesicles, a number of which carried the secretory vesicle-associated membrane-bound protein Rab 27A. In addition, transient upregulation of receptor for advanced glycation end-products (RAGE), an HMGB1 membrane receptor, was found in most epithelial cells of the scarring organ of Corti when extracellular levels of HMGB1 were at their highest. Altogether, these results strongly suggest that, in stressful conditions, Deiters cells liberate HMGB1 to regulate the epithelial reorganization of the injured organ of Corti through engagement of RAGE in neighbouring epithelial cells. “
“Previous results point towards
a lateralization of dorsolateral prefrontal cortex (DLPFC) function in risky decision making. While the right hemisphere seems involved in inhibitory cognitive control of affective impulses, the left DLPFC is crucial in the deliberative processing of information p38 kinase assay relevant for the decision. However, a lack of empirical evidence precludes definitive conclusions. The aim of our study was to determine whether anodal transcranial direct current stimulation (tDCS) over the right DLPFC with cathodal tDCS over the Selleck Metformin lDLPFC (anodal right/cathodal left) or vice versa (anodal left/cathodal right) differentially modulates risk-taking
in a task [the Columbia Card Task (CCT)] specifically engaging affect-charged (Hot CCT) vs. deliberative (Cold CCT) decision making. The facilitating effect of the anodal stimulation on neuronal activity was emphasized by the use of a small anode and a big cathode. To investigate the role of individual differences in risk-taking, participants were either smokers or non-smokers. Anodal left/cathodal right stimulation decreased risk-taking in the ‘cold’ cognition version of the task, in both groups, probably by modulating deliberative processing. In the ‘hot’ version, anodal right/cathodal left stimulation led to opposite effects in smokers and non-smokers, which might be explained by the engagement of the same inhibitory control mechanism: in smokers, improved controllability of risk-seeking impulsivity led to more conservative decisions, while inhibition of risk-aversion in non-smokers resulted in riskier choices.