(C) 2010 Elsevier Ltd. All rights reserved.”
“The synthetic retinoid 13-cis-retinoic acid (13-cis-RA), prescribed for the see more treatment of severe nodular acne, has been linked to an increased incidence of depression. Chronic treatment studies in rodents have shown that 13-cis-RA induces an increase
in depression-related behaviours and a functional uncoupling of the hippocampus and dorsal raphe nucleus (DRN). Changes in the number of serotoninergic neurons in the DRN have been reported in depressed human patients. Given that retinoids have apoptotic effects, we hypothesized that a decrease in the number of serotoninergic neurons in the DRN or median raphe nucleus (MRN) would lead to decreased serotoninergic tone and in turn to the behavioural changes seen with 13-cis-RA administration. Here, we used immunolabelling and unbiased stereological methods to estimate the number of serotonin (5-hydroxytryptamine, 5-HT) neurons in the MRN and DRN of vehicle control and 13-cis-RA-treated
adult mice. In the MRN, the number of 5-HT immunolabelled cells was 1815 +/- 194 in control, compared with 1954 +/- 111 in 13-cis-RA treated tissues. The number of 5-HT immunolabelled cells was much higher in the DRN, with 7148 +/- 377 cells in the control, compared with 7578 +/- 424 in the 13-cis-RA treated group. Further analysis of the DRN revealed that there were no changes in the number of 5-HT neurons within distinct subregions of the DRN. Similarly, changes in the density of serotoninergic neurons or in the volume of the MRN or DRN were not observed in 13-cis-RA treated animals. selleck chemical These data show that apoptotic actions of 13-cis-RA do not occur in vivo at drug concentrations that induce changes in depression-related behaviour and functional uncoupling of the DRN and hippocampus. The potential pro-depressant
behavioural and molecular effects associated with chronic administration of 13-cis-RA may result from changes in serotoninergic activity rather than changes in the number of serotoninergic neurons. (C) 2011 IBRO. Published find more by Elsevier Ltd. All rights reserved.”
“Calsequestrin (CSQ) is the primary calcium buffer within the sarcoplasmic reticulum (SR) of cardiac cells. It has also been identified as a regulator of Ryanodine receptor (RyR) calcium release channels by serving as a SR luminal sensor. When calsequestrin is free and unbound to calcium, it can bind to RyR and desensitize the channel from cytoplasmic calcium activation. In this paper, we study the role of CSQ as a buffer and RyR luminal sensor using a mechanistic model of RyR-CSQ interaction. By using various asymptotic approximations and mean first exit time calculation, we derive a minimal model of a calcium release unit which includes CSQ dependence. Using this model, we then analyze the effect of changing CSQ expression on the calcium release profile and the rate of spontaneous calcium release.