A5021211245- Neuroscience and Neuropharmacology Research
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Ion channel regulation and function
- Erythrocyte Function and Pathophysiology
- Photoreceptor and optogenetics research
- Neural dynamics and brain function
- Receptor Mechanisms and Signaling
- RNA Research and Splicing
- Advanced Fluorescence Microscopy Techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Stress Responses and Cortisol
- Calcium signaling and nucleotide metabolism
- Genetic Neurodegenerative Diseases
- Adipose Tissue and Metabolism
- Tryptophan and brain disorders
- Advanced Memory and Neural Computing
- Calpain Protease Function and Regulation
- RNA regulation and disease
- Neuropeptides and Animal Physiology
- Trace Elements in Health
- Extracellular vesicles in disease
- Adenosine and Purinergic Signaling
- Axon Guidance and Neuronal Signaling
- Nicotinic Acetylcholine Receptors Study
University of Coimbra
2007-2024
University of Copenhagen
2012-2021
Université de Bordeaux
2006-2017
Centre National de la Recherche Scientifique
2006-2017
Institut Interdisciplinaire de Neuroscience
2012-2017
Boston University
2017
Foundation Center
2015
Lundbeck Foundation
2013-2015
Center for Neurosciences
2003
Presynaptic ionotropic glutamate receptors are emerging as key players in the regulation of synaptic transmission. Here we identify GluR7, a kainate receptor (KAR) subunit with no known function brain, an essential presynaptic autoreceptors that facilitate hippocampal mossy fiber GluR7(-/-) mice display markedly reduced short- and long-term potentiation. Our data suggest KARs GluR6/GluR7 heteromers coassemble localized within synapses. We show recombinant exhibit low sensitivity to...
Glutamate is the main excitatory neurotransmitter in central nervous system (CNS) and a major player complex brain functions. Glutamatergic transmission primarily mediated by ionotropic glutamate receptors, which include NMDA, AMPA kainate receptors. However, exerts modulatory actions through family of metabotropic G-protein-coupled receptors (mGluRs). Dysfunctions glutamatergic neurotransmission have been implicated etiology several diseases. Therefore, pharmacological modulation has widely...
SNARE complex assembly constitutes a key step in exocytosis that is rendered Ca 2+ -dependent by interactions with synaptotagmin-1. Two putative sites for synaptotagmin binding have recently been identified SNAP-25 using biochemical methods: one located around the center and another at C-terminal end of bundle. However, it still unclear whether how synaptotagmin-1 × these are involved regulating fast neurotransmitter release. Here, we used electrophysiological techniques high time-resolution...
Progress in understanding the roles of kainate receptors (KARs) synaptic integration, networks, and higher brain function has been hampered by lack selective pharmacological tools. We have found that UBP310 related willardiine derivatives, previously characterized as GluK1 GluK3 KAR antagonists, block postsynaptic KARs at hippocampal mossy fiber (MF) CA3 synapses while sparing AMPA NMDA receptors. further show is an antagonist recombinant GluK2/GluK5 receptors, major population brain....
Abstract Brain-derived neurotrophic factor (BDNF) is an important mediator of long-term synaptic potentiation (LTP) in the hippocampus. The local effects BDNF depend on activation translation activity, which requires delivery transcripts to synapse. In this work, we found that neuronal activity regulates dendritic localization RNA-binding protein heterogeneous nuclear ribonucleoprotein K (hnRNP K) cultured rat hippocampal neurons by stimulating BDNF-Trk signaling. Microarray experiments...
Homeostatic synaptic scaling is a negative feedback response to fluctuations in strength induced by developmental or learning-related processes, which maintains neuronal activity stable. Although several components of the apparatus have been characterized, intrinsic regulatory mechanisms promoting remain largely unknown. MicroRNAs may contribute posttranscriptional control mRNAs implicated different stages scaling, but their role these still undervalued. Here, we report that chronic blockade...
It is currently unknown whether the molecular steps of large dense-core vesicle (LDCV) docking and priming are identical to corresponding reactions in synaptic (SV) exocytosis. Munc13s essential for SV priming, we systematically analyzed their role LDCV exocytosis using chromaffin cells lacking individual isoforms. We show that particularly Munc13-2 plays a fundamental exocytosis, but contrast synapses Munc13s, do not exhibit defect. further demonstrate ubMunc13-2 Munc13-1 confer...
Abstract Age‐associated memory decline is due to variable combinations of genetic and environmental risk factors. How these factors interact drive disease onset currently unknown. Here we begin elucidate the mechanisms by which post‐traumatic stress disorder ( PTSD ) at a young age contributes an increased develop dementia old age. We show that actin nucleator Formin 2 Fmn2) deregulated in Alzheimer's AD patients. Young mice lacking Fmn2 gene exhibit ‐like phenotypes corresponding...
Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] is essential for exocytosis. Classical ways of manipulating PI(4,5)P2 levels are slower than its metabolism, making it difficult to distinguish effects from those metabolites. We developed a membrane-permeant, photoactivatable PI(4,5)P2, which loaded into cells in an inactive form and activated by light, allowing sub-second increases levels. By combining this compound with electrophysiological measurements mouse adrenal chromaffin cells, we...
Synaptotagmins confer calcium-dependence to the exocytosis of secretory vesicles, but how coexpressed synaptotagmins interact remains unclear. We find that synaptotagmin-1 and synaptotagmin-7 when present alone act as standalone fast slow Ca 2+ -sensors for vesicle fusion in mouse chromaffin cells. When together, are found largely non-overlapping clusters on dense-core vesicles. Synaptotagmin-7 stimulates -dependent priming inhibits depriming, it promotes ubMunc13-2- phorbolester-dependent...
Background: Extracellular vesicles (EVs) carry bioactive molecules associated with various biological processes, including miRNAs.In both Huntington's disease (HD) models and human samples, altered expression of miRNAs involved in synapse regulation was reported.Recently, the use EV cargo to reverse phenotypic alterations synaptopathy as end result pathophysiological cascade has become an interesting possibility.Methods: Here, we assessed contribution EVs GABAergic synaptic using a HD model...
Glutamate and NPY have been implicated in hippocampal neuropathology temporal lobe epilepsy. Thus, we investigated the involvement of receptors mediating neuroprotection against excitotoxic insults organotypic cultures rat slices. Exposure slice to 2 microM AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate) induced neuronal degeneration, monitored by propidium iodide uptake, granule cells CA1 pyramidal cells. For dentate cells, selective activation Y1, Y2, or Y5 with 1...
Adenosine is a neuromodulator acting mainly via inhibitory A1 and facilitatory A2A receptors. Whole tissue PCR also identified adenosine A3 receptors in the brain receptor agonists affect CNS neuronal responses viability. However, recent reports failed to detect expression neurons showed that can bind activate We now present evidence for presence of mRNA using single cell analysis laser dissected hippocampal neurons. Western blot are rat nerve terminal membranes. This indicates hippocampus.
Neurotransmitter release depends on the fusion of secretory vesicles with plasma membrane and their contents. The final step displays higher-order Ca(2+) dependence, but also upstream steps depend Ca(2+). After deletion sensor for fast - synaptotagmin-1 slower Ca(2+)-dependent components persist. These findings have provoked working models involving parallel releasable vesicle pools (Parallel Pool Models, PPM) driven by alternative sensors release, no slow acting a pool has been identified....
The RNA binding protein hnRNP K mediates BDNF-induced proteome remodeling at the neuronal synapse.
Abstract Endophilins-A are conserved endocytic adaptors with membrane curvature-sensing and -inducing properties. We show here that, independently of their role in endocytosis, endophilin-A1 endophilin-A2 regulate exocytosis neurosecretory vesicles. The number distribution vesicles were not changed chromaffin cells lacking endophilin-A, yet fast capacitance amperometry measurements revealed reduced exocytosis, smaller vesicle pools altered fusion kinetics. levels distributions the main...
Abstract Evidence for increased calpain activity has been described in the hippocampus of rodent models temporal lobe epilepsy. However, it is not known whether calpains are involved cell death that accompanies seizures. In this work, we characterized activation by examining proteolysis substrates and parallel followed epileptic rats. Male Wistar rats were injected with kainic acid (10 mg/kg) intraperitoneally killed 24 h later, after development grade 5 We observed a strong Fluoro‐Jade...
Protein Interacting with C Kinase 1 (PICK1) is a Bin/Amphiphysin/Rvs (BAR) domain protein involved in AMPA receptor trafficking. Here, we identify selective role for PICK1 the biogenesis of large, dense core vesicles (LDCVs) mouse chromaffin cells. colocalized syntaxin-6, marker immature granules. In cells isolated from knockout (KO) amount exocytosis was reduced, while release kinetics and Ca<sup>2+</sup> sensitivity were unaffected. Vesicle-fusion events had reduced frequency released...