A5088783716- Down syndrome and intellectual disability research
- Genetics and Neurodevelopmental Disorders
- Birth, Development, and Health
- Congenital heart defects research
- Prenatal Screening and Diagnostics
- Genomic variations and chromosomal abnormalities
- Pregnancy and preeclampsia studies
- Ubiquitin and proteasome pathways
- Disability Rights and Representation
- Epigenetics and DNA Methylation
- Autism Spectrum Disorder Research
- Folate and B Vitamins Research
- Gestational Diabetes Research and Management
- Neonatal Respiratory Health Research
- Neonatal and Maternal Infections
- Peptidase Inhibition and Analysis
- Infant Nutrition and Health
- Attention Deficit Hyperactivity Disorder
- Congenital Diaphragmatic Hernia Studies
- Diet and metabolism studies
- Genetic Neurodegenerative Diseases
- Stress Responses and Cortisol
- Preterm Birth and Chorioamnionitis
- Immunodeficiency and Autoimmune Disorders
- Neuroendocrine regulation and behavior
National Human Genome Research Institute
2018-2025
National Institutes of Health
2018-2025
Tufts Medical Center
2013-2023
Tufts Children's Hospital
2013-2020
Sorbonne Paris Cité
2012-2015
Université Paris Cité
1997-2015
University of North Carolina at Chapel Hill
2015
Unit of Functional and Adaptive Biology
2009-2015
Marian Regional Medical Center
2015
Washington University in St. Louis
2015
Individuals with partial HSA21 trisomies and mice MMU16 containing an extra copy of the DYRK1A gene present various alterations in brain morphogenesis. They also learning impairments modeling those encountered Down syndrome. Previous MRI histological analyses a transgenic generated using human YAC construct that contains five genes including reveal is involved, during development, control volume cell density specific regions. Gene dosage correction induces rescue alterations. involved...
Down syndrome (DS) results from triplication of human chromosome 21. Neuropathological hallmarks DS include atypical central nervous system development that manifests prenatally and extends throughout life. As a result, individuals with exhibit cognitive motor deficits have delays in achieving developmental milestones. To determine whether different mouse models recapitulate the prenatal postnatal phenotypes, here we directly compared brain histogenesis, gene expression, behavior over...
The gene Dyrk1a is the mammalian ortholog of Drosophila minibrain. localizes in Down syndrome (DS) critical region chromosome 21q22.2 and a major candidate for behavioral neuronal abnormalities associated with DS. PFC malfunctions are common denominator several neuropsychiatric diseases, including DS, but contribution DYRK1A dysfunctions, particular synaptic basis impairments executive functions reported DS patients, remains obscure. We quantified plasticity, biochemical markers, dendritic...
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...
Anatomical and functional brain abnormalities begin during fetal life in Down syndrome (DS). We hypothesize that novel prenatal treatments can be identified by targeting signaling pathways are consistently perturbed cell types/tissues obtained from human fetuses with DS mouse embryos. analyzed transcriptome data trisomy 21, age sex-matched euploid controls, embryonic day 15.5 forebrains Ts1Cje, Ts65Dn, Dp16 mice. The new datasets were compared to other publicly available humans DS. used the...
Studies in humans with Down syndrome (DS) show that alterations fetal brain development are followed by postnatal deficits neuronal numbers, synaptic plasticity, and cognitive motor function. This same progression is replicated several mouse models of DS. Dp(16)1Yey/+ (hereafter called Dp16) a recently developed model DS which the entire region chromosome 16 homologous to human 21 has been triplicated. As such, Dp16 mice may more closely reproduce neurodevelopmental changes occurring Here,...
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...
Abstract Down syndrome (DS) or trisomy 21 (T21) is present in a significant number of children and adults around the world associated with cognitive medical challenges. Through research, T21 Research Society (T21RS), established 2014, unites worldwide community dedicated to understanding impact on biological systems improving quality life people DS across lifespan. T21RS hosts an international conference every two years support collaboration, dissemination, information sharing for this goal....
Human fetuses with Down syndrome demonstrate abnormal brain growth and reduced neurogenesis. Despite the prenatal onset of phenotype, most therapeutic trials have been conducted in adults. Here, we present evidence for fetal molecular neonatal behavioral alterations Ts1Cje mouse model syndrome. Embryonic day 15.5 hemisphere RNA from embryos (n = 5) wild type littermates was processed hybridized to gene 1.0 ST arrays. Bioinformatic analyses were implemented identify differential pathway...
BACKGROUND: Maternal over- and undernutrition in pregnancy plays a critical role fetal brain development function. The effects of different maternal diet compositions on intrauterine programming the is lesser-explored area. goal this study was to investigate impact two chowmaternal diets gene expression signatures, fetal/neonatal growth, neonatal adult behavior mouse model. METHODS: Throughout lactation, female C57Bl/6J mice were fed one standard, commercially-available chow (pellet vs....
Abstract We investigated gene expression and functional differences between Ts1Cje mice wild‐type ( WT ) littermates in adult cerebral cortex hippocampus. These two brain regions are affected people with D own syndrome, but have not been previously molecularly characterized mice. Total RNA was prepared from the brains of 8–10‐week‐old (n = 6) 5) hybridized to A ffymetrix 1.0 ST mouse arrays. Differentially regulated genes were identified used perform silico analyses better characterize...
Down syndrome (DS) is the most common genetic cause of intellectual disability (ID) in humans with an incidence ∼1:1,000 live births worldwide. It caused by presence extra copy all or a segment long arm human chromosome 21 (trisomy 21). People DS present constellation phenotypic alterations involving organs and organ systems. ID people DS, albeit variable severity. also frequent Alzheimer's disease (AD), ∼50% those will develop AD-related dementia. In last few years, significant progress has...
A yeast artificial chromosome (YAC) transgenic murine model of partial trisomy 21 overexpressing five human genes -- including DYRK1A, which encodes a serine threonine kinase involved in cell cycle control has been shown to present an increase brain weight. We analyzed this new phenotype by measuring total and regional volumes at different ages, using 7 Tesla magnetic resonance imaging volumetric approach. Volumetric measurements showed volume 13.6% adult mice. Changes morphogenesis were...
Abstract Nonchimeric polytransgenic 152F7 mice encompassing four human chromosome 21 genes (DSCR3, DSCR5, TTC3, and DYRK1A) within the Down syndrome critical region present with learning memory impairment. However, no abnormalities were shown by in vitro electrophysiological or neuroanatomical findings hippocampus of mice. To search for molecular changes that may be linked to cognitive impairment, we compared hippocampal protein levels between nontransgenic (WT) a proteomic approach. Protein...
The Ts1Cje model of Down syndrome is particular interest for perinatal studies because affected males are fertile. This permits pups to be carried in wild-type females, which similar human pregnancies. Here we describe the early natural history and growth profiles embryos neonates determine if heart defects present this strain.Pups were studied either on embryonic (E) day 15.5, or from postnatal (P) 3 through weaning P21. PCR amplification targeting neomycin cassette (present Ts1Cje) Sry...