A5024812589- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Neurotransmitter Receptor Influence on Behavior
- Pharmacological Receptor Mechanisms and Effects
- Cannabis and Cannabinoid Research
- Eating Disorders and Behaviors
- Biochemical Analysis and Sensing Techniques
- Regulation of Appetite and Obesity
- Pain Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Epigenetics and DNA Methylation
- Nerve injury and regeneration
- Adipose Tissue and Metabolism
- Genetics and Neurodevelopmental Disorders
- Diet and metabolism studies
- Chemical Synthesis and Analysis
- Genetic Syndromes and Imprinting
- Cancer, Stress, Anesthesia, and Immune Response
- Ion channel regulation and function
- Attention Deficit Hyperactivity Disorder
- Ion Channels and Receptors
- Sleep and Wakefulness Research
- Substance Abuse Treatment and Outcomes
- Pharmacological Effects and Assays
- Signaling Pathways in Disease
Laboratoire de Neurosciences Cognitives et Adaptatives
2016-2025
Université de Strasbourg
2014-2025
Centre National de la Recherche Scientifique
2009-2025
Inserm
1994-2016
Centre National pour la Recherche Scientifique et Technique (CNRST)
2016
Institut de génétique et de biologie moléculaire et cellulaire
2003-2014
Institut de Biologie Moléculaire et Cellulaire
2008-2012
Eurométropole de Strasbourg
2008
Massachusetts General Hospital
2001-2005
Harvard University
2001-2005
Rat oligonucleotide microarrays were used to detect changes in gene expression the dorsal root ganglion (DRG) 3 days following sciatic nerve transection (axotomy). Two comparisons made using two sets of triplicate microarrays, naïve versus and axotomy. Microarray variability was assessed comparison. These results support use a P < 0.05 significance threshold for detecting regulated genes, despite large number hypothesis tests required. For axotomy comparison, 2-fold cut off alone led an...
Activation of ERK (extracellular signal-regulated kinase) MAP (mitogen-activated protein) kinase in dorsal horn neurons the spinal cord by peripheral noxious stimulation contributes to short-term pain hypersensitivity. We investigated activation inflammation and its involvement regulating gene expression contributing inflammatory Injection complete Freund's adjuvant (CFA) into a hindpaw produced persistent sustained superficial layers (laminae I-IIo) horn. CFA also induced an upregulation...
Molecular mechanisms underlying C-fiber stimulation-induced ERK (extracellular signal-regulated kinase) activation in dorsal horn neurons and its contribution to central sensitization have been investigated. In adult rat spinal slice preparations, of primary afferents by a brief exposure capsaicin produces an eightfold 10-fold increase phosphorylation (pERK) superficial neurons. The pERK induction is reduced blockade NMDA, AMPA/kainate, group I metabotropic glutamate receptor, neurokinin-1,...
Large scale sequencing of the human μ-opioid receptor (hMOR) gene has revealed polymorphic mutations that occur within coding region. We have investigated whether N40D in extracellular N-terminal region, N152D third transmembrane domain, and R265H S268P intracellular loop alter functional properties expressed mammalian cells. The was produced at low densities. Binding affinities structurally diverse opioids (morphine, diprenorphine, DAMGO CTOP) main endogenous opioid peptides (β-endorphin,...
Using the mouse delta-opioid receptor cDNA as a probe, we have isolated genomic clones encoding human mu- and kappa-opioid genes. Their organization appears similar to that of delta gene, with exon-intron boundaries located after putative transmembrane domains 1 4. The kappa gene was mapped at position q11-12 in chromosome 8. A full-length has been isolated. cloned expressed COS cells presents typical pharmacological profile is negatively coupled adenylate cyclase. expression mRNA brain,...
In both the spared nerve injury (SNI) and spinal ligation (SNL) rat peripheral neuropathic pain models presynaptic inhibitory effect of mu opioid receptor (MOR) agonist (DAMGO) on primary afferent-evoked excitatory postsynaptic currents (EPSCs) miniature EPSCs in superficial dorsal horn neurons is substantially reduced, but only those cord segments innervated by injured afferents. The two also reduce potassium channel opening action DAMGO lamina II neurons, again receiving afferent input....
In the present study we examine role of transmembrane aromatic residues δ-opioid receptor in ligand recognition. Three-dimensional computer modeling allowed to identify an pocket within helices bundle which spans domains (Tms) III VII and consists tyrosine, phenylalanine, tryptophan residues. Their contribution opioid binding was assessed by single amino acid replacement: Y129F Y129A (Tm III), W173A IV), F218A F222A V), W274A VI), Y308F VII). Scatchard analysis shows that mutant receptors,...
We have used the mouse delta-opioid receptor (mDOR) cDNA to isolate mDOR gene and its human homologue. In both species coding region is interrupted by two introns with conserved exon-intron boundaries located after transmembrane domains 1 4. Using polymerase chain reaction primers based on sequence of cloned (hDOR) gene, we obtained a full length encoding hDOR from SH-SY5Y neuroblastoma cells. The 100% identical genomic 94% at protein level. When expressed in COS cells, displays nanomolar...
Opioids are cationic compounds that mediate their biological action through three highly homologous receptors (mu, delta, and kappa) known to belong the G protein-coupled receptor (GPR) family. The third putative transmembrane domain of opioid contains a conserved aspartate residue is typically found in biogenic amine binding GPRs generally believed form an ion pair with neurotransmitters. Using site-directed mutagenesis, we investigated possibility identical role for this (Asp128) mouse...
Abstract Addiction develops from the gradual adaptation of brain to chronic drug exposure, and involves genetic reprogramming neuronal function. The central extended amygdala (EAc) is a network formed by bed nucleus stria terminalis. This key site controls craving seeking behaviors, has not been investigated at gene regulation level. We used Affymetrix microarrays analyze transcriptional activity in murine EAc, with focus on mu‐opioid receptor‐associated events because these receptors...
Abstract Delta‐selective agonists have been developed to produce potent analgesic compounds with limited side‐effects. DPDPE and deltorphin II are considered prototypes, but their delta‐selectivity in vivo the true ability of delta receptors analgesia remain be demonstrated. Here we performed a parallel analysis mu, combinatorial opioid receptor knockout mice, which found no obvious alteration G‐protein coupling for remaining receptors. We compared behavioural responses two models acute...
ABSTRACT Addiction is a chronic brain disorder. Prolonged abstinence from drugs of abuse involves dysphoria, high stress responsiveness and craving. The neurobiology drug abstinence, however, poorly understood. We previously identified unique set hundred mu‐opioid receptor‐dependent genes in the extended amygdala, key site for hedonic processing brain. Here we examined these candidate either immediately after morphine, nicotine, Δ9‐tetrahydrocannabinol or alcohol, following 4 weeks...
Abstract Addiction is a chronic brain disorder that progressively invades all aspects of personal life. Accordingly, addiction to opiates severely impairs interpersonal relationships, and the resulting social isolation strongly contributes severity chronicity disease. Uncovering new therapeutic strategies address this aspect therefore great clinical relevance. We recently established mouse model heroin in which, following exposure, ‘abstinent’ mice develop strong long‐lasting avoidance...