Biochemical alterations in patients with Down syndrome

Varga, Pál S.; Oláh, Anna V.; Oláh, Éva

doi:10.1556/oh.2008.28327

Cited by 9 publications

(9 citation statements)

References 10 publications

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“…A correlation between protein level and substrate concentration was established in both Ms and Ts males versus control animals and confirmed the parallel, for Cbs , between gene expression level and protein level. Interestingly, the homocysteine level in Ts females was not affected in our study a result similar to some obtained in human T21 patients at the adult stage (80,81) but controversial to others obtained in younger individuals (37). …”

Section: Discussionsupporting

confidence: 84%

A new mouse model for the trisomy of the Abcg1–U2af1 region reveals the complexity of the combinatorial genetic code of down syndrome

Pereira

Magnol

Sahún

et al. 2009

Human Molecular Genetics

105

129

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Mental retardation in Down syndrome (DS), the most frequent trisomy in humans, varies from moderate to severe. Several studies both in human and based on mouse models identified some regions of human chromosome 21 (Hsa21) as linked to cognitive deficits. However, other intervals such as the telomeric region of Hsa21 may contribute to the DS phenotype but their role has not yet been investigated in detail. Here we show that the trisomy of the 12 genes, found in the 0.59 Mb (Abcg1–U2af1) Hsa21 sub-telomeric region, in mice (Ts1Yah) produced defects in novel object recognition, open-field and Y-maze tests, similar to other DS models, but induces an improvement of the hippocampal-dependent spatial memory in the Morris water maze along with enhanced and longer lasting long-term potentiation in vivo in the hippocampus. Overall, we demonstrate the contribution of the Abcg1–U2af1 genetic region to cognitive defect in working and short-term recognition memory in DS models. Increase in copy number of the Abcg1–U2af1 interval leads to an unexpected gain of cognitive function in spatial learning. Expression analysis pinpoints several genes, such as Ndufv3, Wdr4, Pknox1 and Cbs, as candidates whose overexpression in the hippocampus might facilitate learning and memory in Ts1Yah mice. Our work unravels the complexity of combinatorial genetic code modulating different aspect of mental retardation in DS patients. It establishes definitely the contribution of the Abcg1–U2af1 orthologous region to the DS etiology and suggests new modulatory pathways for learning and memory.

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Section: Discussionsupporting

confidence: 84%

A new mouse model for the trisomy of the Abcg1–U2af1 region reveals the complexity of the combinatorial genetic code of down syndrome

Pereira

Magnol

Sahún

et al. 2009

Human Molecular Genetics

105

129

View full text Add to dashboard Cite

show abstract

“…Reynolds (35) found that antioxidant supplementation did not improve the development of children with DS. Interestingly, a study assessing total serum antioxidant activity levels, but in contrast to previous reports, has found no significant difference between control individuals and those with DS (36) . However, increased serum concentrations of lipid peroxidation products, i.e.…”

Section: Discussioncontrasting

confidence: 71%

Erythrocyte phospholipid molecular species and fatty acids of Down syndrome children compared with non-affected siblings

et al. 2014

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The majority of children with Down syndrome (DS) develop Alzheimer's disease (AD) at an early age. Although long-chain n-3 fatty acids (FA) are protective of neurodegeneration, little is known about the FA status in DS. In the present study, we aimed to investigate whether children with DS presented altered plasma and erythrocyte membrane phospholipids (PL) FA composition, when compared with their nonaffected siblings. Venous blood samples were analysed for plasma and erythrocyte membrane FA composition by TLC followed by GC techniques. Lipid molecular species were determined by electrospray ionisation/tandem MS (ESI-MS/MS). FA analysis measured by standard GC showed an increased concentration of MUFA and a decreased concentration of plasmalogens in major PL fractions, but there were no differences in the concentrations of arachidonic acid or DHA. However, as identified by ESI-MS/MS, children with DS had increased levels of the following erythrocyte PL molecular species: 16 : 0 -16 : 0, 16 : 0 -18 : 1 and 16 : 0 -18 : 2n-6, with reduced levels of 16 : 0 -20 : 4n-6 species. Children with DS presented significantly higher levels of MUFA in both plasma and erythrocyte membrane, as well as higher levels of saturated and monounsaturated molecular species. Of interest was the almost double proportion of 16 : 0 -18 : 2n-6 and nearly half the proportion of 16 : 0 -20 : 4n-6 of choline phosphoacylglycerol species in children with DS compared with their non-affected siblings. These significant differences were only revealed by ESI-MS/MS and were not observed in the GC analysis. Further investigations are needed to explore molecular mechanisms and to test the association between the pathophysiology of DS and the risk of AD.

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“…Formimidoyltransferase cyclodeaminase (FTCD) is another gene located on the long arm of chromosome 21 which provides instruction to produce formimimotransferase cyclodeaminase enzyme involved in the metabolism of histidine and the production of folate required for synthesis of purine, pyrimidines and amino acids. Variations in the activities of various enzymes and plasma electrolyte concentrations to differ from normal parameters in DS have previously been reported especially in HSA 21 associated proteins such as S100B [7]. The levels of S100B protein were 4-8 times higher in DS individuals compared to the reference values.…”

Section: Gene-dosage Effectsmentioning

confidence: 83%

Altered Metabolism in Down Syndrome

Al‐Aama¹,

Ahmad²,

Ahmad³

et al. 2015

Health Problems in Down Syndrome

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Down syndrome DS is associated with aberrations in genetic, morphological, biochemical and physiological characteristics. " number of genes located on human chromosome HS" encode proteins which are thought to be involved in numerous metabolic pathways, e.g., phosphofructokinase, cystathionine β-synthase etc. Perturbations of the metabolic pathways may lead to altered drug metabolism in DS individuals. We present a review of metabolic aberrations linked to HS" genes in DS. We particularly focus on drug disposition, efficacy, sensitivity and toxicity of anti-leukaemic agents including methotrexate, glucocorticoids, anthracyclines and cytarabine in DS leukaemia. The different outcomes of therapy due to differential drug response, varied drug toxicity and treatment related mortality in DS leukaemia is a subject of much research and speculation. "ltered drug response in DS individuals may stem from differences in pharmacokinetics, pharmacodynamics and pharmacogenetics. Further large-cohort studies in different age groups dissecting metabolic and molecular pathways involved in drug response may increase our understanding in this regard and stipulate pharmacotherapies in DS.

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Biochemical alterations in patients with Down syndrome

Cited by 9 publications

References 10 publications

A new mouse model for the trisomy of the Abcg1–U2af1 region reveals the complexity of the combinatorial genetic code of down syndrome

A new mouse model for the trisomy of the Abcg1–U2af1 region reveals the complexity of the combinatorial genetic code of down syndrome

Erythrocyte phospholipid molecular species and fatty acids of Down syndrome children compared with non-affected siblings

Altered Metabolism in Down Syndrome

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