A5089526892- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Fatty Acid Research and Health
- Inflammatory mediators and NSAID effects
- Adipose Tissue and Metabolism
- Neuroscience and Neuropharmacology Research
- Tryptophan and brain disorders
- Eicosanoids and Hypertension Pharmacology
- Neurogenesis and neuroplasticity mechanisms
- Mitochondrial Function and Pathology
- S100 Proteins and Annexins
- Cholesterol and Lipid Metabolism
- Immune Response and Inflammation
- Peroxisome Proliferator-Activated Receptors
- Diet and metabolism studies
- Growth Hormone and Insulin-like Growth Factors
- Cardiovascular Function and Risk Factors
- RNA modifications and cancer
- Metabolism and Genetic Disorders
- Chemokine receptors and signaling
- Cardiac Imaging and Diagnostics
- Pluripotent Stem Cells Research
- Dietary Effects on Health
- Cell Adhesion Molecules Research
- Neuropeptides and Animal Physiology
Sorbonne Université
2015-2025
Centre de Recherche Saint-Antoine
2015-2025
Inserm
2013-2025
Hôpital Saint-Antoine
2015-2025
Cairo University
2013
National Institutes of Health
2007-2012
Institute on Aging
2008-2011
National Institute on Aging
2008-2011
Physiologie de la Nutrition et du Comportement Alimentaire
2002-2007
Institut National de la Recherche Agronomique
2003-2005
Recent studies highlight the implication of innate and adaptive immunity in pathophysiology Alzheimer's disease, foster immunotherapy as a promising strategy for its treatment. Vaccines targeting amyloid-β peptide provided encouraging results mouse models, but severe side effects attributed to T cell responses first clinical trial AN1792 underlined need better understanding disease. We previously showed that regulatory cells critically control amyloid-β-specific CD4 + both physiological...
J. Neurochem. (2012) 120 , 292–301. Abstract Like macrophages, microglia are functionally polarized into different phenotypic activation states, referred as classical and alternative. The balance of the two phenotypes may be critical to ensure proper brain homeostasis, altered in pathological such Alzheimer’s disease. We investigated role NADPH oxidase microglial state using p47 phox gp91 ‐deficient mice well apocynin, a inhibitor during neuroinflammation induced by an...
Cyclooxygenases (COX) -1 and -2 are key mediators of the inflammatory response in central nervous system. Since COX-2 is inducible by stimuli, it has been traditionally considered as most appropriate target for anti-inflammatory drugs. However, specific roles COX-1 modulating a neuroinflammatory unclear. Recently, we demonstrated that deficient mice show decreased neuronal damage to lipopolysaccharide (LPS).In this study, investigated role intracerebroventricular-injected LPS (5 mug), model...
Alzheimer9s disease (AD) is a frequent and irreversible age-related neurodegeneration without efficient treatment. Experimental AD in mice responds positively to decreased insulin-like growth factor I (IGF-I) signaling, pathway also implicated aging. Here we aimed protect the aging brain from devastating amyloid pathology by making specifically adult neurons resistant IGF signaling. To achieve that, knocked out neuronal IGF-1R during adulthood APP/PS1 mice. We found that mutants exhibited...
Several epidemiological and preclinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase (COX), reduce the risk of Alzheimer's disease (AD) can lower β-amyloid (Aβ) production neuroinflammation. However, follow-up clinical trials, mostly using selective (COX)-2 inhibitors, failed to show any beneficial effect in AD patients with mild severe cognitive deficits. Recent data indicated COX-1, classically viewed as homeostatic isoform, is localized...
Because brain membranes contain large amounts of docosahexaenoic acid (DHA, 22:6n-3), and as (n-3) PUFA dietary deficiency can lead to impaired attention, learning, memory performance in rodents, we have examined the influence an PUFA-deprived diet on central cholinergic neurotransmission system. We focused several neurochemical parameters frontal cortex hippocampus rats fed PUFA-deficient diet, compared with a control diet. The resulted changes membrane phospholipid compositions both...
Summary Downregulation of insulin‐like growth factor ( IGF ) pathways prolongs lifespan in various species, including mammals. Still, the cellular mechanisms by which signaling controls aging trajectory individual organs are largely unknown. Here, we asked whether suppression ‐I receptor ‐1R) adult stem cells preserves long‐term cell replacement, and this may prevent age‐related functional decline a regenerating tissue. Using neurogenesis as paradigm, showed that conditional knockout ‐1R...
Seminal studies using post-mortem brains of patients with Alzheimer's disease evidenced aberrant insulin-like growth factor 1 receptor (IGF1R) signalling. Addressing causality, work in animal models recently demonstrated that long-term suppression IGF1R signalling alleviates progression and promotes neuroprotection. However, the underlying mechanisms remain largely elusive. Here, we showed genetically ablating neurons ageing brain efficiently protects from neuroinflammation, anxiety memory...
Cyclooxygenases (COX) -1 and -2 are key regulators of innate immune responses. We recently demonstrated that the expression proinflammatory cytokines chemokines is reduced in COX-1 null ( −/− ), increased COX-2 mice compared with their respective wild type controls during lipopolysaccharide (LPS)-induced activation. As involved leukocyte recruitment into inflamed brain, we hypothesized deletion will differentially modulate blood–brain barrier (BBB) permeability response to LPS. In present...
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...
Insulin-like growth factors control numerous processes, namely somatic growth, metabolism and stress resistance, connecting this pathway to aging age-related diseases. factor signaling also impacts on neurogenesis, neuronal survival structural plasticity. Recent reports demonstrated that diminished insulin-like confers increased resistance in brain other tissues. To better understand the role of neuroprotection, we inactivated type-1-receptor forebrain neurons using conditional...
ABSTRACT Growing evidence highlights sex‐related differences in the pathogenesis of Alzheimer's disease (AD). Yet, early impact sex on neuronal activity and microglia hippocampus, a main site memory formation one most vulnerable brain areas AD, remains poorly understood. We thus assessed these issues by using APPPS1 mouse model AD‐like amyloid pathology at pre‐symptomatic stage (5–6 months). Our electrophysiological data point to opposite alterations hippocampal CA1 neurons' basal...
Significance Energy homeostasis is fundamental for the survival of living organisms and contributes to their health, longevity, aging. When food resources are scarce, during experimental calorie restriction, endothermic animals can lower core body temperature. Here, we found that this response regulated by insulin-like growth factor 1 receptor. This demonstrates three main factors affecting aging longevity (calorie reduction signaling, lowered temperature) components same pathway modulates...
Regulation of firing rate homeostasis constitutes a fundamental property central neural circuits. While intracellular Ca 2+ has long been hypothesized to be feedback control signal, the molecular machinery enabling network-wide homeostatic response remains largely unknown. We show that deletion insulin-like growth factor-1 receptor (IGF-1R) limits in inactivity, without altering distribution baseline rates. The deficient was due disruption both postsynaptic and intrinsic plasticity. At...
Growth hormone (GH) and insulinlike growth factor (IGF) promote aging age-related pathologies. Inhibiting this pathway by targeting IGF receptor (IGF-1R) is a promising strategy to extend life span, alleviate diseases, reduce tumor growth. Although anti–IGF-1R agents are being developed, long-term effects of IGF-1R blockade remain unknown. In study, we used ubiquitous inducible knockout (UBIKOR) suppress signaling in all adult tissues screened health extensively. Surprisingly, UBIKOR mice...
Abstract Background Passive immunization with antibodies directed to Aβ decreases brain Aβ/amyloid burden and preserves memory in transgenic mouse models of Alzheimer's disease (AD). This therapeutic strategy is under intense scrutiny clinical studies, but its application limited by neuroinflammatory side effects (autoimmune encephalitis vasogenic edema). Methods We intravenously administered the monoclonal protofibril antibody PFA1 aged (22 month) male female 3 × tg AD mice intermediate or...