Glucocorticoid stress hormones are powerful modulators of brain function and can affect mood and cognitive processes. The hippocampus is a prominent glucocorticoid target and expresses both the... Show moreGlucocorticoid stress hormones are powerful modulators of brain function and can affect mood and cognitive processes. The hippocampus is a prominent glucocorticoid target and expresses both the glucocorticoid receptor (GR: Nr3c1) and the mineralocorticoid receptor (MR: Nr3c2). These nuclear steroid receptors act as ligand-dependent transcription factors. Transcriptional effects of glucocorticoids have often been deduced from bulk mRNA measurements or spatially informed individual gene expression. However, only sparse data exists allowing insights on glucocorticoid-driven gene transcription at the cell type level. Here, we used publicly available single-cell RNA sequencing data to assess the cell-type specificity of GR and MR signaling in the adult mouse hippocampus. The data confirmed that Nr3c1 and Nr3c2 expression differs across neuronal and non-neuronal cell populations. We analyzed co-expression with sex hormones receptors, transcriptional coregulators, and receptors for neurotransmitters and neuropeptides. Our results provide insights in the cellular basis of previous bulk mRNA results and allow the formulation of more defined hypotheses on the effects of glucocorticoids on hippocampal function. Show less
Meijer, F.; Honing, M.; Roor, T.; Toet, S.; Calis, P.; Olofsen, E.; ... ; Dahan, A. 2020
Background: The majority of postoperative patients report moderate to severe pain, possibly related to opioid under-dosing or overdosing during surgery. Objective guidance of opioid dosing using... Show moreBackground: The majority of postoperative patients report moderate to severe pain, possibly related to opioid under-dosing or overdosing during surgery. Objective guidance of opioid dosing using the Nociception Level (NOL) index, a multiparameter artificial intelligence-driven index designed to monitor nociception during surgery, may lead to a more appropriate analgesic regimen, with effects beyond surgery. We tested whether NOL-guided opioid dosing during general anaesthesia results in less postoperative pain.Methods: In this two-centre RCT, 50 patients undergoing abdominal surgery under fentanyl/sevoflurane anaesthesia were randomised to NOL-guided fentanyl dosing or standard care in which fentanyl dosing was based on haemodynamics. The primary endpoint of the study was postoperative pain assessed in the PACU.Results: Median postoperative pain scores were 3.2 (inter-quartile range 1.3-4.3) and 4.8 (3.0-5.3) in NOL-guided and standard care groups, respectively (P=0.006). Postoperative morphine consumption (standard deviation) was 0.06 (0.07) mg kg(-1) (NOL-guided group) and 0.09 (0.09) mg kg(-1) (control group; P=0.204). During surgery, fentanyl dosing was not different between groups (NOL-guided group: 6.4 [4.2] mg kg(-1) vs standard care: 6.0 [2.2] mg kg(-1), P=0.749), although the variation between patients was greater in the NOL-guided group (% coefficient of variation 66% in the NOL-guided group vs 37% in the standard care group).Conclusions: Despite absence of differences in fentanyl and morphine consumption during and after surgery, a 1.6-point improvement in postoperative pain scores was observed in the NOL-guided group. We attribute this to NOL-driven rather than BP- and HR-driven fentanyl dosing during anaesthesia. Show less
