A5051781291- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Endometriosis Research and Treatment
- Neuroscience and Neuropharmacology Research
- Pharmacological Receptor Mechanisms and Effects
- Receptor Mechanisms and Signaling
- Reproductive System and Pregnancy
- Pharmacological Effects and Assays
- Perfectionism, Procrastination, Anxiety Studies
- Mass Spectrometry Techniques and Applications
- Cell Image Analysis Techniques
- Neurotransmitter Receptor Influence on Behavior
- Cannabis and Cannabinoid Research
- Microbial metabolism and enzyme function
- Intestinal and Peritoneal Adhesions
- Apelin-related biomedical research
- Adenosine and Purinergic Signaling
- Uterine Myomas and Treatments
- Single-cell and spatial transcriptomics
- Nerve injury and regeneration
- Cancer Genomics and Diagnostics
- Menstrual Health and Disorders
- Retinal Development and Disorders
- Phytochemicals and Antioxidant Activities
- Cancer, Stress, Anesthesia, and Immune Response
Bayer (Germany)
2014-2023
Bayer (United States)
2021-2023
Institut des Neurosciences Cellulaires et Intégratives
2010-2019
Centre National de la Recherche Scientifique
2011-2019
Université de Strasbourg
2010-2019
Inserm
2008-2011
Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie
2008
Rationale: Despite the importance of inflammation in chronic obstructive pulmonary disease (COPD), immune cell landscape lung tissue patients with mild-moderate has not been well characterized at single-cell and molecular level. Objectives: To define from COPD resolution. Methods: We performed transcriptomic, proteomic, T-cell receptor repertoire analyses on (n = 5, Global Initiative for Chronic Obstructive Lung Disease I or II), emphysema without airflow obstruction 5), end-stage 2),...
ATP-dependent P2X3 receptors play a crucial role in the sensitization of nerve fibers and pathological pain pathways. They are also involved pathways triggering cough may contribute to pathophysiology endometriosis overactive bladder. However, despite strong therapeutic rationale for targeting receptors, preliminary antagonists have been hampered by off-target effects, including severe taste disturbances associated with blocking P2X2/3 receptor heterotrimer. Here we present antagonist,...
The P2X4 receptor is a ligand-gated ion channel that expressed on variety of cell types, especially those involved in inflammatory and immune processes. High-throughput screening led to new class inhibitors with substantial CYP 3A4 induction human hepatocytes. A structure-guided optimization respect decreased pregnane X (PXR) binding was started. It found the introduction larger more polar substituents ether linker less PXR while maintaining inhibitory potency. This translated into...
Genetic analyses in humans and macaques followed by cellular mouse studies demonstrate NPSR1 as a nonhormonal drug target endometriosis.
Transient receptor potential ankyrin 1 (TRPA1) is a voltage-dependent, ligand-gated ion channel, and activation thereof linked to variety of painful conditions. Preclinical studies have demonstrated the role TRPA1 receptors in broad range animal models acute, inflammatory, neuropathic pain. In addition, clinical study using antagonist GRC-17536 (Glenmark Pharmaceuticals) efficacy subgroup patients with diabetic neuropathy. Consequently, there an increasing interest inhibitors as analgesics....
Background Mammalian cells synthesize morphine and the respective biosynthetic pathway has been elucidated. Human neutrophils release this alkaloid into media after exposure to precursors. However, exact role of endogenous in inflammatory processes remains unclear. We postulate that is released during infection can be determined serum patients with severe such as sepsis. Methodology The presence subcellular immunolocalization was investigated by ELISA, mass spectrometry analysis laser...
Morphine is endogenously synthesized in the central nervous system and endogenous dopamine thought to be necessary for morphine formation. As Parkinson's disease results from loss of associated with pain, we considered how regulated untreated l-DOPA-treated parkinsonian brain. However, as cellular origin overall distribution remains obscure pathological adult brain, first characterized morphine-like compound immunoreactive cells rat striatum. We then studied changes immunoreactivity medium...
Abstract Endometriosis is a common gynaecological disease of women in reproductive age, and thought to arise from retrograde menstruation implantation endometrial tissue, mostly into the peritoneal cavity. The condition characterized by chronic, unresolved inflammatory process thereby contributing pain as cardinal symptom endometriosis. Elevated reactive oxygen species (ROS) oxidative stress have been postulated factors endometriosis pathogenesis. We here set out for systematic study...
BackgroundMorphine, the principal active agent in opium, is not restricted to plants, but also present different animal tissues and cell types, including mammalian brain. In fact, its biosynthetic pathway has been elucidated a human neural line. These data suggest role for morphine brain physiology (e.g., neurotransmission), this hypothesis remains matter of debate. Recently, using adrenal neuroendocrine chromaffin model, we have shown presence morphine-6-glucuronide (M6G) secretory granules...
Abstract Background Chronic pelvic pain (CPP) is a high burden for patients and society. It affects 15–24% of women in reproductive age an area unmet medical need. CPP can be caused by wide range visceral diseases such as abdominal infections, gastrointestinal or gynaecological like endometriosis. Despite the need this condition, pharmacological approaches are hampered limited number available methods behavioural evaluation inflammation‐driven animal models pain. Methods The dynamic weight...
Endogenous morphine, morphine-6-glucuronide, and codeine, which are structurally identical to vegetal alkaloids, can be synthesized by mammalian cells from dopamine. However, the role of brain endogenous morphine its derivative compounds is a matter debate, knowledge about distribution lacking. In this study, using validated antibody, we describe precise mapping morphine-like (morphine and/or glucuronides codeine) in mouse brain. First, mass spectrometry approach confirmed presence codeine...
Abstract Morphine, codeine, morphine‐6‐glucuronide, and morphine‐3‐glucuronide are synthesized de novo in mammalian cells the central nervous system. Knowledge on endogenous morphine‐like compound distribution adult mouse brain has been recently improved, new hypotheses have suggested about potential implications physiology. Endogenous compounds shown to be spinal cord, but their localization is unknown. Here we describe of (morphine and/or its glucuronides codeine) cord using a...
Background Lithium is widely used to treat bipolar disorders and displays mood stabilizing properties. In addition, lithium relieves painful cluster headaches has a strong analgesic effect in neuropathic pain rat models. Objectives To investigate the of on cuff model pain. Methods We behavioral pharmacological approaches study single injection wild-type mu opioid receptor (MOR) null cuffed mice. Mass spectrometry enzyme-linked immunosorbent assay allowed measure levels endogenous MOR agonist...
The superior colliculus is a hub for multisensory integration necessary visuo-spatial orientation, control of gaze movements and attention. multiple functions the have prompted hypotheses about its involvement in neuropsychiatric conditions, but to date, this topic has not been addressed experimentally. We describe experiments on genetically modified mice, Isl2-EphA3 knock-in line, that show well-characterized duplication retino-collicular cortico-collicular axonal projections leading...
Background and Purpose Chronic administration of medication can significantly affect metabolic enzymes leading to physiological adaptations. Morphine metabolism in the liver has been extensively studied following acute morphine treatment, but such processes CNS are poorly characterized. Long‐term treatment is limited by development tolerance, resulting a decrease its analgesic effect. Whether or not tolerance affects vivo brain blood–brain barrier (BBB) permeability remains major question....
Morphine is an analgesic alkaloid used to relieve severe pain, and irreversible binding of morphine specific unknown proteins has been previously observed. In the brain, changes in expression energy metabolism enzymes contribute behavioral abnormalities during chronic treatment. Creatine kinase B (CK-B) a key enzyme involved brain metabolism. CK-B also corresponds imidazoline-binding protein I2 which binds dopamine (a precursor biosynthesis) irreversibly. Using biochemical approaches, we...
Mice deficient for the stable tubule only peptide (STOP) display altered dopaminergic neurotransmission associated with severe behavioural defects including disorganized locomotor activity. Endogenous morphine, which is present in nervous tissues and synthesized from dopamine, may contribute to these behavioral alterations since it thought play a role normal pathological neurotransmission.In this study, we showed that STOP null brain structures, cortex, hippocampus, cerebellum spinal cord,...
Endogenous morphine and its derivatives (morphine‐6‐glucuronide [M6G]; morphine‐3‐glucuronide [M3G]) are formed by mammalian cells from dopamine. Changes in the concentrations of endogenous have been demonstrated several pathologies (sepsis, Parkinson's disease, etc.), they might be relevant as pathological markers. While levels detectable using enzyme‐linked immunosorbant assay (ELISA), mass spectrometry (MS) analysis was, so far, only approach to detect quantify M6G. This study describes...