Síndrome de down: aspectos epidemiológicos, genéticos e experimentais

Abstract

Individuals with DS present a low life expectancy. In adulthood, the Alzheimer's disease (AD) contributes to early mortality. Impaired olfactory function and renal dysfunction may be associated with AD. The main cause of AD in DS is the triplication of gene that codes for Amyloid precursor protein (APP), which results in the increase of amyloid beta (Aβ). Vitamin D3 (VD3) can minimize the pathogenic effects of Aβ increasing clearance in peripheral tissues and in the central nervous system (CNS). Objective: To identify the epidemiological profile of individuals with DS in Brazil and genes, located in the critical region of chromosome 21, involved with neurological phenotypes. In addition to evaluate the effects of VD3 supplementation on the kidney and olfactory bulb (OB) in a mouse model of DS. Methods: Data of 10,028 death records (1996-2016) were collected from the informatics Department of the Brazilian Unified Health System (DATASUS). The variables as gender, ethnicity and schooling were defined to verify the level of association with mortality. In the bioinformatics analysis, the database PUBMED was used to select target genes localized on Down syndrome critical region, of which were analyzed in the Database for Annotation Visualization and Integrated Discovery (DAVID) e Gene Ontology (GO). For experimental research 20 B6EiC3Sn Rb(12.Ts171665Dn)2Cje/CjeDnJ female mice, were divided into four experimental groups: control with and without trisomy; VD3 with and without trisomy. Treatment was performed for 10 weeks. In 24ª week the experimental protocol was discontinued. Kidney and OB were collected and processed for histological analysis, immunohistochemistry and Western blotting. Results: There was a positive correlation between the number of death records and the analyzed years. Children under two years of age, regardless of administrative regions, were more susceptible to death. The variables education and ethnicity were associated with mortality. In the Southeast and South regions, individuals of yellow and white ethnicity and some level of education had longer survival. According to bioinformatics prediction, 19 genes located in the critical region showed involvement with neurological disorders. The mouse model for DS presented morphofunctional changes in kidney and O that were attenuated after VD3 supplementation. The treatment also increased the immunostaining of the methylenetetrahydrofolate redudase (MTHFR), caspase-3 p12 and P-glycoprotein (Pgp) proteins; and reduced Aβ42 in the kidney. In OB, VD3 was an important factor for reducing caspase-3 p12 and MTHFR. Conclusion: The mortality record in the population with DS has increased in the last decade and sociodemographic variables are associated with mortality and have repercussions on survival. Some genes located in the critical region in chromosome 21 contribute to neurological dysfunctions and disorders. VD3 supplementation attenuates morphological abnormalities in the kidney and OB affecting the expression of target proteins, in mouse model of DS, minimizing the effects caused by increase of βA42.