A5011768234- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuropeptides and Animal Physiology
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Receptor Mechanisms and Signaling
- Pain Mechanisms and Treatments
- Cancer, Stress, Anesthesia, and Immune Response
- Medicinal Plants and Neuroprotection
- Ion Transport and Channel Regulation
- Botany and Plant Ecology Studies
- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Neonatal Respiratory Health Research
- Cholinesterase and Neurodegenerative Diseases
- Amino Acid Enzymes and Metabolism
- Cell Image Analysis Techniques
- Tryptophan and brain disorders
- Invertebrate Taxonomy and Ecology
- Ecology and Vegetation Dynamics Studies
- Studies on Chitinases and Chitosanases
- 14-3-3 protein interactions
- Advanced Neuroimaging Techniques and Applications
- Lysosomal Storage Disorders Research
Janssen (Belgium)
2019-2024
Institut de génétique et de biologie moléculaire et cellulaire
2020-2021
Université de Strasbourg
2017-2020
Centre National de la Recherche Scientifique
2020
Inserm
2020
KU Leuven
2011-2016
Institute of Pathology and Genetics
2013
Musée National d'Histoire Naturelle
1996
Background Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting memory and cognition. The accompanied by an abnormal deposition of ß-amyloid plaques in brain that contributes to neurodegeneration known induce glial inflammation. Studies APP/PS1 mouse model ß-amyloid-induced neuropathology have suggested a role for inflammasome activation neuroinflammation neuropathology. Methods Here, we evaluated vivo microglia-selective full body signalling several models AD...
The microtubule associated protein tau causes primary and secondary tauopathies by unknown molecular mechanisms. Post-translational O-GlcNAc-ylation of brain proteins was demonstrated here to be beneficial for Tau.P301L mice pharmacological inhibition O-GlcNAc-ase. Chronic treatment ageing mitigated their loss in body-weight improved motor deficits, while the survival 3-fold higher at pre-fixed study endpoint age 9.5 months. Moreover, O-GlcNAc-ase significantly breathing parameters mice,...
Opiates are potent analgesics but their clinical use is limited by side effects including analgesic tolerance and opioid-induced hyperalgesia (OIH). The produce analgesia other adverse through activation of the mu opioid receptor (MOR) encoded Oprm1 gene. However, MOR morphine metabolism involvement in OIH have been little explored. Hence, we examined contribution to comparing morphine-induced wild type (WT) knockout (KO) mice. We found that repeated administration led WT mice not KO absence...
A major challenge in medicine is developing potent pain therapies without the adverse effects of opiates. Neuroinflammation and particular microglial activation have been shown to contribute these effects. However, implication mu opioid receptor (MOR) not known. We developed a novel conditional knockout (cKO) mouse line, wherein MOR deleted microglia. Morphine analgesic tolerance was delayed both sexes cKO mice hot plate assay. Opioid-induced hyperalgesia (OIH) as measured tail immersion...
Stress has been implicated as a risk factor for the severity and progression of sporadic Alzheimer's disease (AD). Early life experiences determine stress responsivity in later life, modulate age-dependent cognitive decline. Therefore, we examined whether early influence AD outcome bigenic mouse model which progressively develops combined tau amyloid pathology (biAT mice).Mice were subjected to either (ELS) or 'positive' handling (EH) postnatally (from day 2 9). In biAT mice, ELS...
Cognitive demise correlates with progressive brain tauopathy in dementing patients. Improved cognition of young Tau.P301L mice contrasts dysfunction later life and remains unexplained (Boekhoorn et al., 2006). To unravel early mechanisms, we composed a correlative time line clinical symptoms, cognitive defects, biochemical pathological traits, including comprehensive analysis dendritic spines specified regions the cortex hippocampus adult mice. Remarkably, have not more, but more mature than...
Abstract Background GSK3β is involved in a wide range of physiological functions, and presumed to act the pathogenesis neurological diseases, from bipolar disorder Alzheimer’s disease (AD). In contrast, GSK3α isozyme remained largely ignored with respect both aspects. Results We generated characterized two mouse strains neuron-specific or total deficiency. Behavioral electrophysiological analysis demonstrated importance neuronal GSK3α, not compensating for impaired cognition reduced LTP....
The stratum lacunosum moleculare (SLM) is the connection hub between entorhinal cortex and hippocampus, two brain regions that are most vulnerable in Alzheimer's disease. We recently identified a specific synaptic deficit of Nectin-3 transgenic models for tauopathy. Here we defined cognitive impairment electrophysiological problems SLM Tau.P301L mice, which corroborated structural defects synapses dendritic spines. Reduced diffusion DiI from ERC to hippocampus indicated defective myelinated...
Cell adhesion molecules are important structural substrates, required for synaptic plasticity and synaptogenesis. CAMs differ widely in their expression throughout different brain regions specific functional roles the remain to be elucidated. Here, we investigated selected cell alterations levels neuronal localization validated mouse models Alzheimer's disease that mimic age-related progression of amyloid accumulation tauopathy. Among analyzed, Nectin-3 was affected most specifically all...
Abstract The two main histopathological hallmarks that characterize Alzheimer’s Disease are the presence of amyloid plaques and neurofibrillary tangles. One current approaches to studying consequences pathology relies on usage transgenic animal models incorporate mutant humanized form precursor protein (hAPP), with progressively developing as they age. However, these mice generally overexpress hAPP facilitate development pathology, which has been suggested elicit pathological...
As a consequence of the discovery an extracellular component responsible for progression tau pathology, immunotherapy is being extensively explored in both preclinical and clinical studies as disease modifying strategy treatment Alzheimer's disease.Describe characteristics anti-phospho (T212/T217) selective antibody PT3 its humanized variant hPT3.By performing different immunization campaigns, large collection antibodies has been generated prioritized. In depth, vitro characterization using...
Abstract The microtubule‐associated protein Tau is responsible for a large group of neurodegenerative disorders, known as tauopathies, including Alzheimer's disease. Tauopathy result from augmented and/or aberrant phosphorylation Tau. Besides aging and various genetic epigenetic defects that remain largely unknown, an important non‐genetic agent contributes hypothermia, eventually caused by anesthesia. Remarkably, tauopathy in brains hibernating mammals not pathogenic, and, because it fully...
Background : The delta opioid receptor (DOR) contributes to pain control, and a major challenge is the identification of DOR populations that control pain, analgesia, tolerance. Astrocytes are known as important cells in pathophysiology chronic many studies report an increased prevalence women. However, implication astrocytic neuropathic well influence sex this activity, remains unknown. Experimental Approach We developed novel conditional knockout (cKO) mouse line wherein deleted astrocytes...
Abstract Alzheimer’s Disease (AD) is a neurodegenerative disease characterized by two main pathological hallmarks: amyloid plaques and intracellular tau neurofibrillary tangles. However, majority of studies focus on the individual pathologies seldom interaction between pathologies. Herein, we present longitudinal neuropathological neurophysiological effects combined amyloid-tau model hippocampal seeding human-derived pathology in APP.PS1/L166P animal model. We statistically assessed both...
The water channel aquaporin 4 (AQP4) contributes to flow and waste removal across the blood-brain barrier its levels, organization localization are perturbed in various neurological diseases, including Alzheimer's Disease. This renders AQP4 a potentially valuable therapeutic target. However, most functional assays aimed at identifying modulators of function performed with primary rodent cells do not consider inter-cellular variations abundance presentation. To address this, we have...
Abstract Background Microglial cells have emerged as key players in the pathogenesis of Alzheimer’s disease (AD). They act a first line defense and fulfil crucial role during brain development circuit homeostasis. Microglia are involved removal debris, control neural activity, regulate synaptic plasticity, synapse pruning. Normal microglial functioning can be impaired by aging, stress, genetic predisposition, provoking pathophysiological turnover towards excessive neuroinflammation,...
Urban and periurban environments do not exert the same attraction to naturalists as wilderness areas. A number of inventories species or groups (fauna flora)have been transferred urban environment starting in 19th Century. revival interest, be it on part scientific community managers, has recently reactivated resulted studies which have revealed some notable faunistic floristic changes. In current practice, inventory methods utilized identify, localize describe natural heritage reveal that...
AD patients suffer epileptogenc defects. Time-line analysis of bigenic biAT mice that co-express APP.V717I and Tau.P301L in neurons develop combined Alzheimer pathology (>10-12 months). Important precocious mortality young (<6 months) with epileptic symptoms was totally absent the parental monogenic mice. Neither amyloid nor tauopathy evident brain Amyloid accumulation developed very similar age, while tau phosphorylation oligomerization more early extensive than age-matched Surprisingly,...
Conjugation of b -N-acetylglucosamine to Ser/Thr residues is a reversible post-translational modification many proteins, controlled by two unique enzymes: O-GlcNAc transferase (OGT) and β -N-acetyl-glucosaminidase (OGA). There physiological pathological repercussions significance remain largely unknown in vivo, particularly CNS. Accumulating amyloid peptides aggravate phosphorylation Tau activation GSK3a/b, modeled our bigenic mice biAT biGT (Terwel et al, 2008). Tau.P301L suffer cognitive...