A5009849379- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- TGF-β signaling in diseases
- S100 Proteins and Annexins
- Cholinesterase and Neurodegenerative Diseases
- Memory and Neural Mechanisms
- Protease and Inhibitor Mechanisms
- Mitochondrial Function and Pathology
- Receptor Mechanisms and Signaling
- Nitric Oxide and Endothelin Effects
- Medicinal Plants and Neuroprotection
- Blood Coagulation and Thrombosis Mechanisms
- Traumatic Brain Injury and Neurovascular Disturbances
- Computational Drug Discovery Methods
- Bone Metabolism and Diseases
- Parkinson's Disease Mechanisms and Treatments
- Nerve injury and regeneration
- Ion channel regulation and function
- Inflammatory Bowel Disease
- Neurological Disorders and Treatments
- Nuclear Receptors and Signaling
- Neurogenesis and neuroplasticity mechanisms
- Nematode management and characterization studies
- Anesthesia and Neurotoxicity Research
Centre Hospitalier Universitaire de Clermont-Ferrand
2024-2025
Grenoble Institute of Neurosciences
2012-2024
Inserm
2012-2024
Université Grenoble Alpes
2012-2024
Association François Aupetit
2023
Centre National de la Recherche Scientifique
2002-2021
CEA Grenoble
2012-2021
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2009-2021
Institut National de Recherche en Santé Publique
2018
Laboratoire de Psychologie et NeuroCognition
2017
Tau is a microtubule-associated protein well known for its stabilization of microtubules in axons. Recently, it has emerged that tau participates synaptic function as part the molecular pathway leading to amyloid-beta (Aβ)-driven synaptotoxicity context Alzheimer's disease. Here, we report implication profound functional modification associated with plasticity. By exposing murine cultured cortical neurons pharmacological activation, induced translocation endogenous from dendritic...
N-methyl-D-aspartate receptors (NMDARs) are critical for synaptic plasticity that underlies learning and memory. But, they have also been described as a common source of neuronal damage during stroke neurodegenerative diseases. Several studies sug gested cellular location NMDARs (synaptic or extrasynaptic) is key parameter controlling their effect on viability. The aim the study was to understand relation between these two pools determine implication in both beneficial and/or deleterious...
Recent data showed that glutamate toxicity in primary cortical cultures is mediated by nitric oxide. In order to investigate the effect of inhibition NO synthase on focal cerebral ischaemia rats, we studied histological consequences a middle artery (MCA) occlusion after post-operative treatment with NG-nitro-L-arginine methyl ester, an inhibitor oxide synthase. We found significant reduction (-43%) and striatal (-25%) necrotic volumes induced MCA occlusion, indicating synthesis plays...
Acute brain injuries have been identified as a risk factor for developing Alzheimer's disease (AD). Because glutamate plays pivotal role in these pathologies, we studied the influence of receptor activation on amyloid-β (Aβ) production primary cultures cortical neurons. We found that sublethal NMDA increased and secretion Aβ. This effect was preceded by an expression neuronal Kunitz protease inhibitory domain (KPI) containing precursor protein (KPI-APP) followed shift from α-secretase to...
IN the present study, we examine involvement of L-arginine-nitric oxide pathway in seizure activity termination. Convulsions were induced reproducibly by intracerebroventricular administration N-methyl-D-aspartate to conscious mice. The duration was increased inhibition NO-pathway or injection methylene blue, an inhibitor guanylate cyclase activity. This reversed co-administration L-arginine guanosine 3':5' cyclic monophosphate (cGMP). These results suggest that nitric produced response NMDA...
Calcium is a key mediator controlling essential neuronal functions depending on electrical activity. Altered calcium homeostasis affects metabolism of amyloid precursor protein (APP), leading to increased production β-amyloid (Aβ), and contributing the initiation Alzheimer's disease (AD). A linkage between excessive glutamate receptor activation Aβ release was established, recent reports suggest that synaptic extrasynaptic NMDA (NMDAR) may have distinct consequences in plasticity, gene...
Oligomeric forms of amyloid-forming proteins are believed to be the principal initiating bioactive species in many neurodegenerative disorders, including Alzheimer's disease (AD). Amyloid-β (Aβ) oligomers implicated AD-associated phosphorylation and aggregation microtubule-associated protein tau. To investigate specific molecular pathways activated by different assemblies, we isolated various Aβ from Tg2576 mice, which a model for AD. We found that Aβ*56, 56-kDa oligomer is detected before...
Amyloid-β (Aβ) drives the synaptic impairment and dendritic spine loss characteristic of Alzheimer's disease (AD), but how Aβ affects actin cytoskeleton remains unknown contentious. The actin-binding protein, cofilin-1 (cof1), is a major regulator dynamics in spines, subject to phospho-regulation by multiple pathways, including Rho-associated protein kinase (ROCK) pathway. While cof1 implicated as driver synaptotoxicity early phases AD pathophysiology, questions remain about molecular...
The sequence of cellular dysfunctions in preclinical Alzheimer's disease must be understood if we are to plot new therapeutic routes. Hippocampal neuronal hyperactivity is one the earliest events occurring during stages both humans and mouse models. most common hypothesis describes amyloid-β accumulation as triggering factor but effects this cascade leading cognitive decline remain unclear. In mice, previously showed that amyloid-β-dependent TRPA1 channel activation triggers hippocampal...
Recent evidence has shown that even mild mutations in the Huntingtin gene are associated with late-onset Huntington's disease (HD) disrupt various aspects of human neurodevelopment. To determine whether these seemingly subtle early defects affect adult neural function, we investigated circuit physiology newborn HD mice. During first postnatal week, mice have less cortical layer 2/3 excitatory synaptic activity than wild-type mice, express fewer glutamatergic receptors, and show sensorimotor...
The glial cell line-derived neurotrophic factor (GDNF) is first characterized for its trophic activity on dopaminergic neurons. Recent data suggested that GDNF could modulate the neuronal death induced by ischemia. purpose of this study was to characterize influence cultured cortical neurons subjected two paradigms injury (necrosis and apoptosis) have been identified during cerebral ischemia determine molecular mechanisms involved. First, we demonstrated both astrocytes express mRNA protein...
In the brain, expression of pleiotropic cytokine interleukin-6 (IL-6) is enhanced in various chronic or acute central nervous system disorders. However, significance IL-6 production such neuropathologic states remains controversial. The present study investigated role after cerebral ischemia. First, authors showed that focal ischemia rats early up-regulated mRNA, without affecting transcription its receptors (IL-6Ralpha and gp130). Similarly, striatal injection N-methyl-D-aspartate (NMDA)...
Abstract: We have reported previously that posttreatment with N G ‐nitro‐L‐arginine methyl ester (L‐NAME), an inhibitor of the nitric oxide synthase, reduced volume cortical and striatal infarct induced by middle cerebral artery occlusion in rats. In present study, we investigated mechanisms which L‐NAME (3 mg/kg i.p.) is neuroprotective this model ischemia. First, shown reversal effect a coinjection L‐arginine. Second, order to determine mechanism exacerbates neuronal damage produced focal...
Accumulation of the amyloid-β peptide (Aβ) in brain is crucial for development Alzheimer's disease. Expression transforming growth factor-β1 (TGF-β1), an immunosuppressive cytokine, has been correlated vivowith Aβ accumulation transgenic mice and recently with clearance by activated microglia. Here, we demonstrate that TGF-β1 drives production Aβ40/42 astrocytes leading to mice. First, induces overexpression amyloid precursor protein (APP) but not neurons, involving a highly conserved...
Excessive synaptic loss is thought to be one of the earliest events in Alzheimer's disease (AD). However, key mechanisms that maintain plasticity synapses during adulthood or initiate synapse dysfunction AD remain unknown. Recent studies suggest astrocytes contribute functional changes observed and play a major role but behavior involvement early phases remained largely undefined.We measure astrocytic calcium activity mouse CA1 hippocampus stratum radiatum both global population at single...
Abstract Microtubules play fundamental roles in the maintenance of neuronal processes and synaptic function plasticity. While dynamic microtubules are mainly composed tyrosinated tubulin, long-lived contain detyrosinated suggesting that tubulin tyrosination/detyrosination cycle is a key player microtubule dynamics homeostasis, conditions go awry neurodegenerative diseases. In cycle, C-terminal tyrosine α-tubulin removed by carboxypeptidases re-added ligase (TTL). Here we show TTL...
Abstract Background Faecal calprotectin (Fcal) and magnetic resonance imaging (MRI) could be used as non-invasive tools to monitor mucosal transmural healing, respectively, in Crohn’s disease (CD). We assessed the agreement between Fcal MRI detecting active CD explore complementarity of these predicting long-term outcomes. Methods Using pooled data from two prospective studies, we included patients with who underwent both testing within 7 days. was performed without bowel cleansing or enema...
Various studies describe increased concentrations of transforming growth factor-β (TGF-β) in brain tissue after acute injury. However, the role endogenously produced TGF-β damage to CNS remains be clearly established. Here, authors examine influence an episode cerebral ischemia by injecting a soluble type II receptor fused with Fc region human immunoglobulin (TβRIIs-Fc). First, this molecular construct was characterized as selective antagonist TGF-β. Then, tested its ability reverse effect 1...
Serine proteases play a key role in the fundamental biology of central nervous system (CNS), and recent data suggest their involvement pathophysiology neurodegenerative diseases. Little is known about physiological regulation these CNS. Among multiple growth factors present brain, transforming factor beta1 (TGF-beta1) has been described as an injury-related factor. However, its beneficial or deleterious remains unclear. In study, we investigated influence TGF-beta1 apoptosis necrosis, two...
Neuronal death after ischemia-induced brain damage depends largely upon the activation of N-methyl-D-aspartate (NMDA) excitatory glutamate receptor that is a target for many putative neuroprotective agents. Whereas NMDA receptors mediate ischemic damage, blocking them deleterious in humans. Here, authors investigated whether nitrous oxide or xenon, which are gaseous anesthetics with remarkably safe clinical profile have been recently demonstrated as effective inhibitors receptor, may reduce...
The anaphylatoxin C3a is a potent inflammatory polypeptide released at sites of complement activation. To test whether might alter neuronal outcome following an ischemic insult, we determined the effects purified human on murine primary cortical cell cultures exposed to apoptotic or excitotoxic paradigms. prevented neither serum deprivation-induced death, nor AMPA/kainate-mediated excitotoxicity. However, in mixed neurons and astrocytes, dose-dependently protected against NMDA toxicity (47%...