A5047802985- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Animal Virus Infections Studies
- Tryptophan and brain disorders
- Neurogenesis and neuroplasticity mechanisms
- Plant Virus Research Studies
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
- Stress Responses and Cortisol
- Nerve injury and regeneration
- Herpesvirus Infections and Treatments
- Adipose Tissue and Metabolism
- Nitric Oxide and Endothelin Effects
- RNA modifications and cancer
- Cancer Mechanisms and Therapy
- RNA Interference and Gene Delivery
- Neurogenetic and Muscular Disorders Research
- Virus-based gene therapy research
- Ubiquitin and proteasome pathways
- Congenital heart defects research
- Immune cells in cancer
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Nuclear Receptors and Signaling
Université de Caen Normandie
2024
Centre Hospitalier Universitaire de Caen
2024
Institut du Fer à Moulin
2015-2023
Inserm
2010-2023
Sorbonne Université
2015-2023
NYU Langone Health
2023
Université Sorbonne Nouvelle
2020
Centre National de la Recherche Scientifique
1985-2014
Institut de Biologie de l'École Normale Supérieure
1999-2014
École Normale Supérieure - PSL
1996-2011
In several brain regions, microglia actively promote neuronal apoptosis during development. However, molecular actors leading to trigger death remain mostly unknown. Here, we show that, in the developing hippocampus, apoptotic neurons are contacted by expressing both integrin CD11b and immunoreceptor DAP12. We demonstrate that developmental decreases mice deficient for or addition, function-blocking antibodies directed against decrease when injected into wild-type neonates, but have no...
Several proteins are expressed in both immune and nervous systems. However, their putative nonimmune functions the brain remain poorly understood. KARAP/DAP12 is a transmembrane polypeptide associated with cell-surface receptors hematopoeitic cells. Its mutation humans induces Nasu-Hakola disease, characterized by presenile dementia demyelinization. alteration of white matter occurs months after onset neuropsychiatric symptoms, suggesting that other neuronal alterations occur early phases...
Fine-tuning of neuronal activity was thought to be a neuron-autonomous mechanism until the discovery that astrocytes are active players synaptic transmission. The involvement has changed our understanding roles non-neuronal cells and shed new light on regulation activity. Microglial macrophages brain they have been mostly investigated as immune cells. However recent data discussed in this review support notion that, similarly astrocytes, microglia involved For instance, most, if not all,...
Maturation of functional neuronal circuits during central nervous system development relies on sophisticated mechanisms. First, axonal and dendritic growth should reach appropriate targets for correct synapse elaboration. Second, pruning death are required to eliminate redundant or inappropriate connections. Serotonin, in addition its role as a neurotransmitter, actively participates postnatal establishment refinement brain wiring mammals. Brain resident macrophages, that is, microglia, also...
Epidemiological studies have linked maternal infection during pregnancy to later development of neuropsychiatric disorders in the offspring. In mice, experimental inflammation embryonic impairs behavioral and cognitive performances adulthood. Synaptic dysfunctions may be at origin impairments, however link between prenatal synaptic defects remains established.In this study, we show that alteration microglial function, including inflammation, induces delayed dysfunction adult. DAP12 is a...
Mechanisms inducing neuronal death at defined times during embryogenesis remain enigmatic. We show in explants that a developmental switch occurs between embryonic day 12 (E12) and E13 rats is 72-48 hr before programmed cell death. Half the motoneurons isolated from peripheral tissues E12 escape death, whereas 90% of enter program. The surrounding somite commits to This effect requires macrophage cells, mimicked by tumor necrosis factor α (TNFα), inhibited anti-TNFα antibodies. In vivo ,...
Major depression is a psychiatric disorder with complex etiology. About 30% of depressive patients are resistant to antidepressants that currently available, likely because they only target the monoaminergic systems. Thus, identification novel larger action spectrum urgently required. Epidemiological data indicate high comorbidity between metabolic and disorders, particularly obesity depression. We used well-characterized anxiety/depressive-like mouse model consisting continuous input...
Abstract Spinal muscular atrophy (SMA) is among the most common recessive autosomal diseases and characterized by loss of spinal motor neurons. A gene termed ‘Survival Motor Neurons' (SMN) has been identified as SMA‐determining gene. Recent work indicates involvement SMN protein its associated SIP1 in spliceosomal snRNP biogenesis. However, function remains unknown. Here, we have studied subcellular localization rat cord more generally central nervous system (CNS), light fluorescence...
Nitric oxide (NO) is a diffusible second messenger with great variety of functions in the brain. NO produced by three isoforms synthase (NOS), NOS1, NOS2, and NOS3. Although broad agreement exists regarding expression NOS1 NOS3 neurons endothelial cells, pattern NOS2 still controversial remains elusive. We have now generated novel transgenic mouse that expresses fluorescent reporter tdTomato CRE recombinase under control Nos2 gene regulatory regions. Such tool allows reliable tracking tissue...
Macrophages can either promote or resolve inflammatory responses, and their polarization state is modulated by peripheral serotonin (5-hydroxytryptamine [5-HT]). In fact, pro- anti-inflammatory macrophages differ in the expression of receptors, with 5-HT2B 5-HT7 restricted to M-CSF-primed monocyte-derived (M-MØ). drives acquisition profibrotic functions M-MØ, whereas prevents degeneration spinal cord mononuclear phagocytes modulates motility murine microglial processes. Because mediates...
Abstract The inhibitory glycine receptor is a pentameric membrane protein composed of α and β subunits. In the postsynaptic membrane, copurifying peripheral gephyrin are clustered underneath glycine‐releasing nerve terminals. Here, we describe expression neonatal adult subunit isoforms α1 α2 during in vitro differentiation rat spinal neurons. Analysis by immunoassays reverse transcriptase—polymerase chain reaction showed that mRNA levels exhibited marked increase from 1 to 5 days , i.e....
Abstract Recent studies have demonstrated that nerve growth factor (NGF) induces apoptosis of several cell types in the central nervous system through its low‐affinity p75 neurotrophin receptor (p75 NTR ). To test effect NGF on embryonic motoneuron survival, we developed an organotypic culture which allowed vitro development intact rat spinal cords. In our system, neural tubes were taken and cultured at E13, just before onset physiological death. After 2 days (DIV), motoneurons underwent...
Abstract Severe peripheral infections induce an adaptive sickness behavior and innate immune reaction in various organs including the brain. On long term, persistent alteration of microglia, brain cells, is associated with increased risk psychiatric disorders. It thus critical to identify genes mechanisms controlling intensity duration neuroinflammation induced by challenges. We tested hypothesis that 5‐HT 2B receptor, main serotonin receptor expressed might represent a valuable candidate ....
Infantile spinal muscular atrophy (SMA) is caused by mutations in the survival motor neuron (SMN)1 gene. We investigated role of human (h) SMN protein on cell death PC12 and Rat-1 cells. hSMN prolonged cells deprived trophic support induced to die activation proto-oncogene c-Myc, similar magnitude as Bcl-2 or IAP-2. While was ineffective inhibiting apoptosis ultraviolet light (UV) etoposide treatment proliferating cells, a protective effect observed terminally NGF/dBcAMP-differentiated...