A5061958213- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Neuropeptides and Animal Physiology
- Memory and Neural Mechanisms
- Ion channel regulation and function
- Hypothalamic control of reproductive hormones
- Receptor Mechanisms and Signaling
- Genetic Neurodegenerative Diseases
- Neurogenesis and neuroplasticity mechanisms
- MicroRNA in disease regulation
- Advanced biosensing and bioanalysis techniques
- Nerve injury and regeneration
- Epilepsy research and treatment
- Pancreatic function and diabetes
- Treatment of Major Depression
- Adipose Tissue and Metabolism
- Stress Responses and Cortisol
- RNA Interference and Gene Delivery
- Cholinesterase and Neurodegenerative Diseases
- Peptidase Inhibition and Analysis
- Amino Acid Enzymes and Metabolism
- Tryptophan and brain disorders
- Cardiac electrophysiology and arrhythmias
- Biotin and Related Studies
- Genetics and Neurodevelopmental Disorders
Institut de Pharmacologie Moléculaire et Cellulaire
2012-2024
Centre National de la Recherche Scientifique
2012-2024
Inserm
2016-2024
Université Côte d'Azur
2014-2018
Fondation pour la Recherche Médicale
2012
In Alzheimer disease (AD), the perturbation of endoplasmic reticulum (ER) calcium (Ca²⁺) homeostasis has been linked to presenilins, catalytic core in γ-secretase complexes cleaving amyloid precursor protein (APP), thereby generating amyloid-β (Aβ) peptides. Here we investigate whether APP contributes ER Ca²⁺ and could turn influence Aβ production. We show that overexpression wild-type human (APP(695)), or harboring Swedish double mutation (APP(swe)) triggers increased ryanodine receptor...
Abstract N‐methyl‐D‐aspartate receptors (NMDARs) are critical for the maturation and plasticity of glutamatergic synapses. In hippocampus, NMDARs mainly contain GluN2A and/or GluN2B regulatory subunits. The amyloid precursor protein (APP) has emerged as a putative regulator NMDARs, but impact this interaction to their function is largely unknown. By combining patch‐clamp electrophysiology molecular approaches, we unravel dual mechanism by which APP controls GluN2B‐NMDARs, depending on life...
We have described a novel antidepressant peptide, spadin, that acts by blocking the TWIK-related-potassium channel, type 1 (TREK-1). Here, we examined possible mechanisms of action spadin at both molecular and cellular levels.Effects were measured in primary cultures neurons or tissues from mice injected i.v. with spadin. Western blots, qPCR, histochemical electrophysiological techniques used.In vitro, increased neuronal membrane potential activated MAPK PI3K signalling pathways, time-...
Depression is a devastating mental disorder that affects 20% of the population worldwide. Despite their proven efficacy, antidepressants present delayed onset action and serious adverse effects. Seven years ago, we described spadin (PE 12-28) as promising endogenous peptide with antidepressant activity. Spadin specifically blocks TREK-1 channel. Previously, showed in vivo that, activity disappeared beyond 7h after administration. In order to improve stability bioavailability, screened...
Although the advent of Cas9 technology has expanded our ability to precisely edit genome, manipulating microRNAs in vivo been shown be particularly challenging, especially brain. Here, we sought generate novel tools aiming at targeting and efficiently downregulating defined species a cell-specific manner so that their function discrete neuronal networks could investigated. Focusing on miR-124, microRNA highly expressed mammalian brain transcribed from three independent chromosomal loci,...
Inhibition of the potassium channels TREK-1 by spadin (SPA) is currently thought to be a promising therapeutic target for treatment depression. Since these are expressed in pancreatic β -cells, we investigated their role control insulin secretion and glucose homeostasis. In this study, confirmed expression secreting MIN6-B1 -cell line mouse islets. We found that blockade SPA potentiated induced chloride dependent membrane depolarization. decrease resting potential (<mml:math...
NMDA receptors (NMDARs) are ionotropic crucial for brain information processing. Yet, evidence also supports an ion-flux-independent signaling mode mediating synaptic long-term depression (LTD) and spine shrinkage. Here, we identify AETA (Aη), amyloid-β precursor protein (APP) cleavage product, as NMDAR modulator with the unique dual regulatory capacity to impact both modes. inhibits activity by competing co-agonist induces intracellular conformational modification of GluN1 subunits. This...
The background potassium channel TREK-1 has been shown to be a potent target for depression treatment. Indeed, deletion of this in mice resulted resistant phenotype. association with the sorting protein sortilin prompted us investigate behavior deleted from gene encoding (Sort1-/-). To characterize consequences on activity, we combined behavioral, electrophysiological and biochemical approaches performed vivo vitro. Analyses Sort1-/- revealed that they display: (1) corticosterone-independent...
Although depression is the most common mood disorder, only one third of patients are treated with success. Finding new targets, drugs, and also drug intake way main challenges in field. Several years ago, we identified a target TWIK-related potassium channel-1 (TREK-1) channel, more recently, have discovered peptide 17 amino acids antidepressant properties. This peptide, that called spadin, can be considered as concept design. Spadin derives from larger resulting to posttranslational...
The neuropeptide neurotensin (NT) elicits numerous pharmacological effects through three different receptors (NTSR1, NTSR2, and NTSR3 also called sortilin). Pharmacological approaches generation of NTSR1 NTSR2-deficient mice allowed to determine the NT-induced antipsychotic like behavior, inhibitory weak fear memory nociceptive signaling in a rat formalin tonic pain model NTSR1. Conversely, NT on thermal nociceptions were mediated by NTSR2. However, role NTSR3/sortilin neurotensinergic...
Alzheimer's disease (AD) is a progressive memory loss and cognitive dysfunction brain disorder brought on by the dysfunctional amyloid precursor protein (APP) processing clearance of APP peptides. Increased levels lead to production AD-related peptides including intracellular domain (AICD) beta (Aβ), consequently modify intrinsic excitability hippocampal CA1 pyramidal neurons, synaptic activity, impair plasticity at CA1-CA3 synapses. The goal present study build computational models that...
N-methyl-D-aspartate receptors (NMDARs) are critical for the maturation and plasticity of glutamatergic synapses. In hippocampus, NMDARs mainly contain GluN2A and/or GluN2B regulatory subunits. The amyloid precursor protein (APP) has emerged as a putative regulator NMDARs, but impact this interaction to their function is largely unknown. By combining patch-clamp electrophysiology molecular approaches, we unravel dual mechanism by which APP controls GluN2B-NMDARs, depending on life stage. We...
NMDA receptors (NMDARs) are ionotropic crucial for brain information processing. Yet, evidence also supports an ion flux-independent signaling mode mediating synaptic long-term depression (LTD) and spine shrinkage. Here, we identify AETA (Aη), amyloid-b precursor protein (APP) cleavage product, as NMDAR modulator with the unique dual regulatory capacity to impact both modes. inhibits activity by competing co-agonist induces intracellular conformational modification of GluN1 subunits. This...