Vitamin D increases the Caspase-3 p12, MTHFR, and P-glycoprotein reducing amyloid-β in the kidney of a mouse model for Down syndrome.

Aims: Renal dysfunction has been reported in individuals with Down syndrome (DS); however, the causes and mechanisms involved remain unknown. Here, we present a proposal for how the triplication of the amyloid beta precursor protein (APP) and, mainly the amyloid β peptide 1-42 (Aβ) can favor the development of renal abnormalities in DS. We evaluated the effects of vitamin D (VD) supplementation on morphofunctional aspects and the repercussions on the presence and localization of Aβ, methylenetetrahydrofolate reductase (MTHFR), caspase-3 p12, and P-glycoprotein (Pgp) in the renal tissue of DS mouse model.

Main Methods: Twenty female mice (14-week-old) belonging to the B6EiC3Sn-Rb(12.Ts171665Dn)2Cje/CjeDnJ lineage were divided into four experimental groups (n = 5/group): common diet; trisomy (Ts) and wild-type (Wt); and high doses VD, Ts, and Wt). All the groups were treated for 10 weeks. At 24 weeks, the protocol experimental was interrupted. The kidney was weighed, collected, and processed for immunochemical analysis for Aβ, Caspase-3 p12, MTHFR, and Pgp proteins. All data were analyzed statistically.

Key Findings: Our results showed that VD promoted an increase in caspase-3 p12, MTHFR, and Pgp, and consequently contributed to reduced Aβ in the renal tissue of a mouse model of DS. Furthermore, VD treatment affected the plasma creatinine and urea levels and contributed to the attenuation of the dilation of Bowman's space observed in trisomic mice.

Significance: Finally, the results showed that VD may activate specific mechanisms involved in reduced Aβ and tissue repair in the kidneys of a mouse model for Down syndrome.