Pleiotropic effects of trisomy and pharmacologic modulation on structural, functional, molecular, and genetic systems in a Down syndrome mouse model.

Down syndrome (DS) is characterized by skeletal and brain structural malformations, cognitive impairment, altered hippocampal metabolite concentration and gene expression imbalance. These alterations were usually investigated separately, and the potential rescuing effects of green tea extracts enriched in epigallocatechin-3-gallate (GTE-EGCG) provided disparate results due to different experimental conditions. We overcame these limitations by conducting the first longitudinal controlled experiment evaluating genotype and GTE-EGCG prenatal chronic treatment effects before and after treatment discontinuation. Our findings revealed that the Ts65Dn mouse model reflected the pleiotropic nature of DS, exhibiting brachycephalic skull, ventriculomegaly, neurodevelopmental delay, hyperactivity, and impaired memory robustness with altered hippocampal metabolite concentration and gene expression. GTE-EGCG treatment modulated most systems simultaneously but did not rescue DS phenotypes. On the contrary, the treatment exacerbated trisomic phenotypes including body weight, tibia microarchitecture, neurodevelopment, adult cognition, and metabolite concentration, not supporting the therapeutic use of GTE-EGCG as a prenatal chronic treatment. Our results highlight the importance of longitudinal experiments assessing the co-modulation of multiple systems throughout development when characterizing preclinical models in complex disorders and evaluating the pleiotropic effects and general safety of pharmacological treatments.

Integrative health risk assessment of air pollution in the northwest of Spain.

Levels, origins and potential risks due to different air pollutants (ozone, SO2 and particle-borne metals) in NW Spain were investigated in eight locations affected by different emission sources. All monitored locations suffered the influence of traffic and industrial emissions, being this influence more important in urban locations. Although average values of the estimated hazard index (HI) due to particle-borne metals showed values lower than one, maximum values of this parameter exceeded this safety limit in urban locations. In general, Ni and As were identified as those metals most contributing to the HI. Furthermore, the presence of industrial emission episodes produced a significant increase in the magnitude of the HI in two of the seven urban areas. Therefore, the frequency and intensity of these episodes should be further investigated. Finally, levels of airborne and particle-borne pollutants were integrated with the aim of providing a comprehensive assessment of health risk. According to an established indexing system, air quality can be classified from good to moderate, being the southern urban locations (the most densely populated and industrialised ones) presenting the worst values. However, either the high or the low influence of acute and chronic-effect pollutants on air quality depends on the location.