Browsing by Author "Dierssen, Mara"

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    Behavioral Phenotyping for Down Syndrome in Mice
    (Wiley, 2020-09) Roper, Randall J.; Goodlett, Charles R.; Martínez de Lagrán, María; Dierssen, Mara; Biology, School of Science
    Down syndrome (DS) is the most frequent genetic cause of intellectual disability, characterized by alterations in different behavioral symptom domains: neurodevelopment, motor behavior, and cognition. As mouse models have the potential to generate data regarding the neurological basis for the specific behavioral profile of DS, and may indicate pharmacological treatments with the potential to affect their behavioral phenotype, it is important to be able to assess disease-relevant behavioral traits in animal models in order to provide biological plausibility to the potential findings. The field is at a juncture that requires assessments that may effectively translate the findings acquired in mouse models to humans with DS. In this article, behavioral tests are described that are relevant to the domains affected in DS. A neurodevelopmental behavioral screen, the balance beam test, and the Multivariate Concentric Square Field test to assess multiple behavioral phenotypes and locomotion are described, discussing the ways to merge these findings to more fully understand cognitive strengths and weaknesses in this population. New directions for approaches to cognitive assessment in mice and humans are discussed.
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    Correction to: Specific Susceptibility to COVID-19 in Adults with Down Syndrome
    (Springer, 2021-05-04) Illouz, Tomer; Biragyn, Arya; Frenkel-Morgenstern, Milana; Weissberg, Orly; Gorohovski, Alessandro; Merzon, Eugene; Green, Ilan; Iulita, Florencia; Flores-Aguilar, Lisi; Dierssen, Mara; De Toma, Ilario; Lifshitz, Hefziba; Antonarakis, Stylianos E.; Yu, Eugene; Herault, Yann; Potier, Marie-Claude; Botté, Alexandra; Roper, Randall; Sredni, Benjamin; Sarid, Ronit; London, Jacqueline; Mobley, William; Strydom, Andre; Okun, Eitan; Biology, School of Science
    The current SARS-CoV-2 outbreak, which causes COVID-19, is particularly devastating for individuals with chronic medical conditions, in particular those with Down Syndrome (DS) who often exhibit a higher prevalence of respiratory tract infections, immune dysregulation and potential complications. The incidence of Alzheimer’s disease (AD) is much higher in DS than in the general population, possibly increasing further the risk of COVID-19 infection and its complications. Here we provide a biological overview with regard to specific susceptibility of individuals with DS to SARS-CoV-2 infection as well as data from a recent survey on the prevalence of COVID-19 among them. We see an urgent need to protect people with DS, especially those with AD, from COVID-19 and future pandemics and focus on developing protective measures, which also include interventions by health systems worldwide for reducing the negative social effects of long-term isolation and increased periods of hospitalization.
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    Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome
    (Springer Nature, 2021-02-25) Starbuck, John M.; Llambrich, Sergi; Gonzàlez, Rubèn; Albaigès, Julia; Sarlé, Anna; Wouters, Jens; González, Alejandro; Sevillano, Xavier; Sharpe, James; De La Torre, Rafael; Dierssen, Mara; Vande Velde, Greetje; Martínez‑Abadías, Neus; Robert H. McKinney School of Law
    Trisomy of human chromosome 21 (Down syndrome, DS) alters development of multiple organ systems, including the face and underlying skeleton. Besides causing stigmata, these facial dysmorphologies can impair vital functions such as hearing, breathing, mastication, and health. To investigate the therapeutic potential of green tea extracts containing epigallocatechin-3-gallate (GTE-EGCG) for alleviating facial dysmorphologies associated with DS, we performed an experimental study with continued pre- and postnatal treatment with two doses of GTE-EGCG supplementation in a mouse model of DS, and an observational study of children with DS whose parents administered EGCG as a green tea supplement. We evaluated the effect of high (100 mg/kg/day) or low doses (30 mg/kg/day) of GTE-EGCG, administered from embryonic day 9 to post-natal day 29, on the facial skeletal development in the Ts65Dn mouse model. In a cross-sectional observational study, we assessed the facial shape in DS and evaluated the effects of self-medication with green tea extracts in children from 0 to 18 years old. The main outcomes are 3D quantitative morphometric measures of the face, acquired either with micro-computed tomography (animal study) or photogrammetry (human study). The lowest experimentally tested GTE-EGCG dose improved the facial skeleton morphology in a mouse model of DS. In humans, GTE-EGCG supplementation was associated with reduced facial dysmorphology in children with DS when treatment was administered during the first 3 years of life. However, higher GTE-EGCG dosing disrupted normal development and increased facial dysmorphology in both trisomic and euploid mice. We conclude that GTE-EGCG modulates facial development with dose-dependent effects. Considering the potentially detrimental effects observed in mice, the therapeutic relevance of controlled GTE-EGCG administration towards reducing facial dysmorphology in young children with Down syndrome has yet to be confirmed by clinical studies.
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    Immune Dysregulation and the Increased Risk of Complications and Mortality Following Respiratory Tract Infections in Adults With Down Syndrome
    (Sage, 2021-01) Illouz, Tomer; Biragyn, Arya; Iulita, Maria Florencia; Flores-Aguilar, Lisi; Dierssen, Mara; De Toma, Ilario; Antonarakis, Stylianos E.; Yu, Eugene; Herault, Yann; Potier, Marie-Claude; Botté, Alexandra; Roper, Randall; Sredni, Benjamin; London, Jacqueline; Mobley, William; Strydom, Andre; Okun, Eitan; Medicine, School of Medicine
    The risk of severe outcomes following respiratory tract infections is significantly increased in individuals over 60 years, especially in those with chronic medical conditions, i.e., hypertension, diabetes, cardiovascular disease, dementia, chronic respiratory disease, and cancer. Down Syndrome (DS), the most prevalent intellectual disability, is caused by trisomy-21 in ~1:750 live births worldwide. Over the past few decades, a substantial body of evidence has accumulated, pointing at the occurrence of alterations, impairments, and subsequently dysfunction of the various components of the immune system in individuals with DS. This associates with increased vulnerability to respiratory tract infections in this population, such as the influenza virus, respiratory syncytial virus, SARS-CoV-2 (COVID-19), and bacterial pneumonias. To emphasize this link, here we comprehensively review the immunobiology of DS and its contribution to higher susceptibility to severe illness and mortality from respiratory tract infections.