A5006366415- Neurogenetic and Muscular Disorders Research
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA modifications and cancer
- Cholesterol and Lipid Metabolism
- Neuroscience and Neuropharmacology Research
- RNA regulation and disease
- Muscle Physiology and Disorders
- Nuclear Receptors and Signaling
- MicroRNA in disease regulation
- Spinal Dysraphism and Malformations
- Hormonal Regulation and Hypertension
- HIV Research and Treatment
- Nerve injury and regeneration
- Adenosine and Purinergic Signaling
- RNA and protein synthesis mechanisms
- Immune cells in cancer
- Peroxisome Proliferator-Activated Receptors
- Parkinson's Disease Mechanisms and Treatments
- Virus-based gene therapy research
- Lysosomal Storage Disorders Research
- Family and Disability Support Research
- melanin and skin pigmentation
- Sphingolipid Metabolism and Signaling
- Neurogenesis and neuroplasticity mechanisms
- 14-3-3 protein interactions
Sorbonne Université
2010-2024
Inserm
2010-2024
Centre National de la Recherche Scientifique
2010-2024
Institut du Cerveau
2015-2023
Assistance Publique – Hôpitaux de Paris
2023
Allen Institute for Brain Science
2020
Délégation Paris 5
2012-2019
Université Paris Cité
2012-2019
Toxicologie, Pharmacologie et Signalisation Cellulaire
2015
Centre National pour la Recherche Scientifique et Technique (CNRST)
2013
Abnormalities in neuronal cholesterol homeostasis have been suspected or observed several neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and Huntington's disease. However, it has not demonstrated whether an increased abundance of neurons vivo contributes to neurodegeneration. To address this issue, we used RNA interference methodology inhibit the expression 24-hydroxylase, encoded by Cyp46a1 gene, hippocampus normal mice. Cholesterol 24-hydroxylase controls...
Using transcriptomics, anatomical studies, imaging and ELISA, Morin-Brureau et al. examine microglia in patients with temporal lobe epilepsies. In highly sclerotic regions such as CA1, the anti-inflammatory cytokine IL-10 regulates microglial phenotype. Seizures induce a transient phenotype associated secretion of inflammatory cytokines including human CXCL8.
Microglia exhibit multiple, phenotype-dependent motility patterns often triggered by purinergic stimuli. However, little data exist on of human microglia in pathological situations. Here we examine stained with a fluorescent lectin tissue slices from female and male epileptic patients diagnosed mesial temporal lobe epilepsy or cortical glioma (peritumoral cortex). Microglial shape varied ramified to amoeboid cells predominantly regions high neuronal loss closer tumor. Live imaging revealed...
Spinal muscular atrophy (SMA), a recessive neurodegenerative disease, is characterized by the selective loss of spinal motor neurons. No available therapy exists for SMA, which represents one leading genetic causes death in childhood. SMA caused mutation survival-of-motor-neuron 1 ( SMN1 ) gene, to quantitative defect survival-motor-neuron (SMN) protein expression. All patients retain or more copies SMN 2 modulates disease severity producing small amount stable protein. We reported recently...
Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by the selective loss of spinal motor neurons due to depletion survival neuron (SMN) protein. No therapy currently available for SMA, which represents leading genetic cause death in childhood. In present study, we report that insulin-like growth factor-1 receptor (<i>Igf-1r</i>) gene expression enhanced cords SMA-like mice. The reduction expression, either at physiological (through physical exercise) or level, resulted...
In humans, spinal cord lesions induce not only major motor and neurovegetative deficits but also severe neuropathic pain which is mostly resistant to classical analgesics. Better treatments can be expected from precise characterization of underlying physiopathological mechanisms. This led us thoroughly investigate (i) mechanical thermal sensory alterations, (ii) responses acute with drugs having patent or potential anti-allodynic properties (iii) the spinal/ganglion expression transcripts...
The real impact of physical exercise parameters, i.e. intensity, type contraction and solicited energetic metabolism, on neuroprotection in the specific context neurodegeneration remains poorly explored. In this study behavioural, biochemical cellular analyses were conducted to compare effects two different long-term protocols, high intensity swimming low running, motor units a 3 spinal muscular atrophy (SMA)-like mouse model. Our data revealed preferential SMA-induced death intermediate...
Elevations in neuronal cholesterol have been associated with several degenerative diseases. An enhanced excitability and synchronous firing surviving neurons are among the sequels of death these diseases also some epileptic syndromes. Here, we attempted to increase levels, using a short hairpin RNA suppress expression enzyme cytochrome P450 family 46, subfamily A, polypeptide 1 gene (CYP46A1). This protein hydroxylates so facilitates transmembrane extrusion. A CYP46A1construction coupled...
The deletion of microtubule-associated protein stable tubule only polypeptide (STOP) leads to neuroanatomical, biochemical and severe behavioral alterations in mice, partly alleviated by antipsychotics. Therefore, STOP knockout (KO) mice have been proposed as a model some schizophrenia-like symptoms. Preliminary data showed decreased brain serotonin (5-HT) tissue levels KO mice. As literature demonstrate various interactions between proteins 5-HT, we characterized features the serotonergic...
Spinal Muscular Atrophy (SMA), an autosomal recessive neurodegenerative disease characterized by the loss of spinal-cord motor-neurons, is caused mutations on Survival-of-Motor Neuron (SMN)-1 gene. The expression SMN2, a SMN1 gene copy, partially compensates for disruption due to exon-7 excision in 90% transcripts subsequently explaining strong clinical heterogeneity. Several alterations energy metabolism, like glucose intolerance and hyperlipidemia, have been reported SMA at both systemic...
Key points The present study provides evidence that the cardiomyopathy observed in spinal muscular atrophy (SMA) model mice is mainly due to intrinsic cardiac alteration but not autonomic impairment. We demonstrated a non‐pathological sympathetic activity on heart of type 2 SMA‐like mice, which likely counteracts dramatic function, such as arrhythmia and reduced rate. for first time physical exercise partially restores conduction efficiency, prevents fibrosis, attenuates defects protein...
Abstract Lipid homeostasis is dysregulated in some neurodegenerative diseases and after brain injuries due to excess glutamate or lack of oxygen. However the kinetics cell specificity dysregulation different groups lipids during excitotoxic neuronal death are not clear. Here we examined changes induced by injecting kainic acid ( KA ) into CA 1 region mouse hippocampus. We compared loss glial proliferation with lipid‐related transcripts markers for lipid groups, over 12 days ‐treatment. As...
<title>Abstract</title> A growing body of evidence suggests a correlation between cholesterol metabolism and the pathogenesis Parkinson's disease (PD). We others have demonstrated that activation 24-hydroxylase enzyme, CYP46A1, responsible for converting to 24S-hydroxycholesterol (24-OHC) in brain, is an effective therapeutic strategy several neurodegenerative diseases as Alzheimer's disease, Huntington’s spinocerebellar ataxia type 3. This approach has overexpression CYP46A1 can reduce...
Cholesterol 24-hydroxylase (CYP46A1) is an exclusively neuronal cytochrome P450 enzyme responsible for converting cholesterol into 24S-hydroxycholesterol, which serves as the primary pathway eliminating in brain. We and others have shown that increased activity of CYP46A1 leads to reduced levels has a positive effect on cognition. Therefore, we hypothesized could be potential therapeutic target Niemann-Pick type C (NPC) disease, rare fatal neurodegenerative disorder, characterized by...