A5004951073- Down syndrome and intellectual disability research
- Genetics and Neurodevelopmental Disorders
- Congenital heart defects research
- Genomic variations and chromosomal abnormalities
- Alzheimer's disease research and treatments
- Ubiquitin and proteasome pathways
- Autism Spectrum Disorder Research
- Cardiovascular Function and Risk Factors
- Signaling Pathways in Disease
- Frailty in Older Adults
- Microtubule and mitosis dynamics
- 14-3-3 protein interactions
- Real-time simulation and control systems
- Chromosomal and Genetic Variations
- Genomics and Chromatin Dynamics
- Hearing, Cochlea, Tinnitus, Genetics
- Cancer-related gene regulation
- Animal Genetics and Reproduction
- Cerebral Palsy and Movement Disorders
- Genomics and Rare Diseases
- Cardiac Ischemia and Reperfusion
- Neurogenesis and neuroplasticity mechanisms
- Gene expression and cancer classification
- Pneumonia and Respiratory Infections
- Neonatal and fetal brain pathology
Université de Strasbourg
2013-2025
Inserm
2014-2025
Centre National de la Recherche Scientifique
2013-2025
Institut de génétique et de biologie moléculaire et cellulaire
2014-2025
Institut Clinique de la Souris
2011-2025
Institut de Biologie Moléculaire et Cellulaire
2022
Transgene (France)
2006-2009
Université d'Orléans
2007-2009
Immunologie et Neurogénétique Expérimentales et Moléculaires
2008
Oklahoma Medical Research Foundation
1988
Trisomy for human chromosome 21 results in Down syndrome (DS), which is among the most complex genetic perturbations leading to intellectual disability. Accumulating data suggest that overexpression of dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A), a critical pathogenic mechanisms deficit.Here we show green tea flavonol epigallocatechin-gallate (EGCG), DYRK1A inhibitor, rescues cognitive deficits both segmental trisomy 16 (Ts65Dn) and transgenic mice...
Down syndrome (DS) is the most frequent genetic disorder leading to intellectual disabilities and caused by three copies of human chromosome 21. Mouse models are widely used better understand physiopathology in DS or test new therapeutic approaches. The older mouse trisomic Ts65Dn Ts1Cje mice. They display deficits similar those observed people, such as behavior cognition neuronal abnormalities. model currently for further assessment candidate drugs. In both models, trisomy was induced...
An imbalance between inhibitory and excitatory neurotransmission has been proposed to contribute altered brain function in individuals with Down syndrome (DS). Gamma-aminobutyric acid (GABA) is the major neurotransmitter central nervous system accordingly treatment GABA-A antagonists can efficiently restore cognitive functions of Ts65Dn mice, a genetic model for DS. However, are also convulsant which preclude their use therapeutic intervention DS individuals. Here, we have evaluated safer...
Mental retardation in Down syndrome (DS), the most frequent trisomy humans, varies from moderate to severe. Several studies both human and based on mouse models identified some regions of chromosome 21 (Hsa21) as linked cognitive deficits. However, other intervals such telomeric region Hsa21 may contribute DS phenotype but their role has not yet been investigated detail. Here we show that 12 genes, found 0.59 Mb (Abcg1–U2af1) sub-telomeric region, mice (Ts1Yah) produced defects novel object...
Growing evidence supports the implication of DYRK1A in development cognitive deficits seen Down syndrome (DS) and Alzheimer's disease (AD). We here demonstrate that pharmacological inhibition brain is able to correct recognition memory three DS mouse models with increasing genetic complexity [Tg(Dyrk1a), Ts65Dn, Dp1Yey], all expressing an extra copy Dyrk1a Overexpressed accumulates cytoplasm at synapse. Treatment inhibitor leucettine L41 leads normalization activity corrects novel object...
Cognitive impairment in Down syndrome (DS) has been linked to increased synaptic inhibition. The underlying mechanisms remain unknown, but memory deficits are rescued DS mouse models by drugs targeting GABA receptors. Similarly, administration of epigallocatechin gallate (EGCG)-containing extracts rescues cognitive phenotypes Ts65Dn mice, potentially through pathway. Some developmental and alterations have traced expression the serine-threonine kinase DYRK1A on Hsa21. To better understand...
ABSTRACT Down syndrome (DS) is caused by trisomy of human chromosome 21 (Hsa21). The understanding genotype–phenotype relationships, the identification driver genes and various proofs concept for therapeutics have benefited from mouse models. premier model, named Ts(1716)65Dn/J (Ts65Dn), displayed phenotypes related to DS features. It carries an additional minichromosome with Mir155 Zbtb21 region 16, homologous Hsa21, encompassing around 90 genes, fused centromeric part 17 Pisd-ps2/Scaf8...
Down syndrome (DS) is the most common condition with intellectual disability and caused by trisomy of Homo sapiens chromosome 21 (HSA21). The increased dosage genes on HSA21 associated early neurodevelopmental changes subsequently at adult age development Alzheimer-like cognitive decline. However, molecular mechanisms promoting brain pathology along aging are still missing. novel Ts66Yah model represents an evolution Ts65Dn, used in characterizing progression degeneration, it manifest...
Down syndrome is a common genetic disorder caused by trisomy of chromosome 21. Brain development in affected foetuses might be improved through prenatal treatment. One potential target DYRK1A, multifunctional kinase encoded 21 that, when overexpressed, alters neuronal excitation-inhibition balance and increases GAD67 interneuron density. We used green tea extract enriched EGCG to inhibit DYRK1A function only during gestation transgenic mice overexpressing Dyrk1a (mBACtgDyrk1a). Adult treated...
Decrease of GABAergic transmission has been proposed to improve memory functions. Indeed, inverse agonists selective for α 5 GABA-A-benzodiazepine receptors ( 5IA) have promnesiant activity. Interestingly, we recently shown that 5IA can rescue cognitive deficits in Ts65Dn mice, a Down syndrome mouse model with altered transmission. Here, studied the impact chronic treatment on gene expression hippocampus and control euploid mice after being trained Morris water maze task. In increased IEGs...
The trisomy of human chromosome 21 (Hsa21), which causes Down syndrome (DS), is the most common viable aneuploidy. In contrast to trisomy, complete monosomy (M21) Hsa21 lethal, and only partial or mosaic seen. Both conditions lead variable physiological abnormalities with constant intellectual disability, locomotor deficits, altered muscle tone. To search for dosage-sensitive genes involved in DS M21 phenotypes, we created two new mouse models: Ts3Yah carrying a tandem duplication Ms3Yah...
Down syndrome (DS) is the most common genetic form of intellectual disability caused by presence an additional copy human chromosome 21 (Hsa21). To provide novel insights into genotype-phenotype correlations, we used standardized behavioural tests, magnetic resonance imaging and hippocampal gene expression to screen several DS mouse models for 16 region homologous Hsa21. First, unravelled interactions between different regions how they contribute significantly altering outcome phenotypes in...
Hyperhomocysteinemia, characterized by increased plasma homocysteine level, is associated with an risk of atherosclerosis. On the contrary, patients Down syndrome appear to be protected from development We previously found a deleterious effect hyperhomocysteinemia on expression DYRK1A, Down-syndrome-associated kinase. As DYRK1A and low level have been syndrome, we aimed analyze its over-expression metabolism in mice.Effects were examined biochemical analysis methionine metabolites, real-time...
Excessive GABAergic inhibition contributes to cognitive dysfunctions in Down syndrome (DS). Selective negative allosteric modulators (NAMs) of α5-containing GABAA receptors such as the α5 inverse agonist (α5IA) restore learning and memory deficits Ts65Dn mice, a model DS. In this study we have assessed long-lasting effects α5IA on vivo LTP behaviour mice.We made recordings for six consecutive days freely moving mice their wild-type littermates, treated with vehicle or α5IA. parallel, were by...
Neurodegenerative diseases, including Alzheimer's and Parkinson's disease, are characterized by increased protein aggregation in the brain, progressive neuronal loss, inflammation, neurogenesis impairment. We analyzed effects of a new purine derivative drug, PDD005, attenuating mechanisms involved pathogenesis neurodegenerative using both vivo vitro models. show that PDD005 is distributed to brain can rescue cognitive deficits associated with aging mice. Treatment prevents impairment...
Chromosome 21 DYRK1A kinase is associated with a variety of neuronal diseases including Down syndrome. However, the functional impact this at synapse level remains unclear. We studied mouse model that incorporated YAC 152F7 (570 kb), encoding six chromosome genes DYRK1A. The mice displayed learning difficulties but their N-methyl-D-aspartate (NMDA)-dependent synaptic long-term potentiation indistinguishable from non-transgenic animals. have demonstrated presynaptic form NMDA-independent...