Biology subjects

Decraene, C.

Publications and source records attributed to Decraene, C..

4 recordsLinked to original sources

bioRxiv2025

Repeated restraint stress-induced increase in post-surgical somatosensory hypersensitivity and affective responding is mediated by β-adrenergic receptor activation and spinal NLRP3-IL1β signalling in male rats

Pre-surgical stress is a well-recognised risk factor for persistent post-surgical pain, and while the precise underlying neurobiological mechanisms remain unknown, neuro-immune interactions are believed to play a pivotal role. Here, we investigated the effect of repeated restraint stress (RRS) on post-surgical somatosensory hypersensitivity and affective responding in male rats and examined underlying mechanisms mediating these effects. We showed that RRS induced behavioural despair in the forced swim test, reduced body weight gain and elevated faecal corticosterone levels in male Sprague-Dawley rats. Following paw-incision surgery, animals pre-exposed to RRS exhibited exacerbated mechanical and heat hypersensitivity, pain-related aversion, and anxiety-like behaviour compared to non-stress counterparts. RNAseq analysis revealed alterations in glial and neuro-immune pathways in the dorsal horn of the spinal cord in the RRS + paw incision group compared to paw incision alone, data further confirmed by increased microglial activity and inflammatory gene expression (iba1, itgam, il-1{beta} and nlrp3). Intrathecal administration of IL-1Ra or MCC950 (an NLRP3 inhibitor) attenuated the RRS-induced increase in pain-related aversion and mechanical hypersensitivity post-surgery. Chronic administration of RU486, a glucocorticoid receptor antagonist, prevented RRS-induced despair-like behaviour but did not alter the effects of RRS on pain-related aversion or mechanical hypersensitivity post-surgery. In contrast, chronic administration of propranolol, a {beta}-adrenergic receptor antagonist and sympathetic nervous system inhibitor, not only prevented the RRS-induced despair-like behaviour but also attenuated exacerbation of mechanical hypersensitivity, pain-related aversion, and anxiety-like behaviour post-surgery. These findings suggest that RRS exacerbates and prolongs post-surgical somatosensory and affective pain responding via {beta}-adrenergic receptor activation and increased spinal microglial NLRP3-IL1{beta} signalling. These data provide further insight into the mechanisms by which chronic stress and mood disorders exacerbate and prolong post-surgical pain.

neuroscience↗

bioRxiv2025

Designing new natural-mimetic phosphatidic acid: aversatile and innovative synthetic strategy forglycerophospholipid research

Glycerophospholipids (GPLs) play important roles in cellular compartmentalization and signaling. Among them, phosphatidic acids (PA) exist as many distinct species depending on acyl chain composition, each one potentially displaying unique signaling function. Although the signaling functions of PA have already been demonstrated in multiple cellular processes, the specific roles of individual PA species remain obscure due to a lack of appropriate tools. Indeed, current synthetic PA analogues fail to preserve all the functions of natural PA. To circumvent these limitations, we developed a novel synthetic approach to produce PA analogues without compromising structural integrity of acyl chains. Moreover, addition of a clickable moiety allowed flexible grafting of different molecules to PA analogues for various biological applications. Hence, this innovation also provides powerful tools to investigate specific biological activities of individual PA species, with potential applications in unraveling complex GPL-mediated signaling pathways.

neuroscience↗

bioRxiv2022

Functional genomic mechanisms of opioids: a systematic review of animal and human studies

In the past two decades, over-prescription of opioids for pain management has driven a steep increase in opioid use disorder (OUD) and death by overdose, exerting a dramatic toll on western countries. OUD is a chronic relapsing disease associated with a lifetime struggle to control drug consumption, suggesting that opioids trigger long-lasting brain adaptations, notably through functional genomic and epigenomic mechanisms. Current understanding of these processes, however, remain scarce, and have not been previously reviewed systematically. To do so, the goal of the present work was to synthesize current knowledge on genome-wide transcriptomic and epigenetic mechanisms of opioid action, in primate and rodent species. Using a prospectively registered methodology, comprehensive literature searches were completed in PubMed, Embase, and Web of Science. Of the 2709 articles identified, 73 met our inclusion criteria and were considered for qualitative analysis. Focusing on the 5 most studied nervous system structures (nucleus accumbens, frontal cortex, whole striatum, dorsal striatum, spinal cord; 44 articles), we also conducted a quantitative analysis of differentially expressed genes, in an effort to identify a putative core transcriptional signature of opioids. Only one gene, Cdkn1a, was consistently identified in eleven studies, and globally, our results unveil surprisingly low consistency across published work, even when considering most recent single-cell approaches. Analysis of putative sources of variability detected significant contributions from species, brain structure, duration of opioid exposure, strain, time-point of analysis, and batch effects, but not type of opioid. To go beyond those limitations, we leveraged threshold-free methods to illustrate how genome-wide comparisons may generate new findings and hypotheses. Finally, we discuss current methodological development in the field, and their implication for future research and, ultimately, better care.

neuroscience↗

bioRxiv2021

Dysfunction of exocytosis causes catecholamine hypersecretion in patient with pheochromocytoma

Pheochromocytoma (Pheo) is a neuroendocrine tumor that develops from chromaffin cells of the adrenal medulla, and is responsible of an excess of catecholamines secretion leading to severe clinical symptoms such as hypertension, elevated stroke risk and various cardiovascular complications. Surprisingly, hypersecretory activity of Pheo has never been explored at the cellular and molecular levels from individual tumor cells. In the present study, we have combined catecholamine secretion measurement by carbon fiber amperometry on human tumor cells directly cultured from freshly resected Pheo, with the analysis by mass spectrometry of the exocytotic proteins differentially expressed between the tumor and the matched adjacent non-tumor tissue. Catecholamine secretion recordings from individual Pheo cells obtained from most patients reveal a higher number of exocytic events per cell associated with faster kinetic parameters. Accordingly, we unravel significant tumor-associated modifications in the expression of key proteins involved in different steps of the calcium-regulated exocytic pathway. Altogether, our findings indicate that dysfunction of the calcium-regulated exocytosis at the level of individual Pheo cell is a cause of the tumor-associated hypersecretion of catecholamines.

cancer biology↗