Alterations in the Glycan Composition of Serum Glycoproteins in Attention-Deficit Hyperactivity Disorder

Abstract

Changes in protein glycosylation are associated with most biological processes, and the importance of glycomic analysis in the research of disorders is constantly increasing, including in the neurodevelopmental field. We glycoprofiled sera in 10 children with attention-deficit hyperactivity disorder (ADHD) and 10 matching healthy controls for 3 types of samples: whole serum, sera after depletion of abundant proteins (albumin and IgG), and isolated IgG. The analytical methods used were a lectin-based glycoprotein microarray enabling high-throughput glycan analysis and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) as a standard method for the identification of glycan structures. For microarray analysis, the samples printed on microarray slides were incubated with biotinylated lectins and detected using the fluorescent conjugate of streptavidin by a microarray scanner. In the ADHD patient samples, we found increased antennary fucosylation, decreased di-/triantennary N-glycans with bisecting N-acetylglucosamine (GlcNAc), and decreased α2-3 sialylation. The results obtained by both independent methods were consistent. The study’s sample size and design do not allow far-reaching conclusions to be drawn. In any case, there is a strong demand for a better and more comprehensive diagnosis of ADHD, and the obtained results emphasize that the presented approach brings new horizons to studying functional associations of glycan alterations in ADHD.

Metabolomic Markers in Attention-Deficit/Hyperactivity Disorder (ADHD) among Children and Adolescents—A Systematic Review

“…At this stage, 80 clinically relevant studies were identified for full-text review. Sequentially, 21 of these were excluded for various reasons: 6 studies which identified potentially predictive prenatal markers for ADHD [29][30][31][32][33][34]; 3 which comprised exclusively adult samples [35][36][37], as well as 1 study that included both children and adults without separately presenting differences between healthy children and those with ADHD [38]; 5 studies that did not measure the metabolites themselves [39][40][41][42][43]; 2 that were based on glycomic markers [44,45]; 2 for which the full text could not be obtained [46,47]; 1 study which compared ADHD children divided on the basis of inflammatory marker levels, with no control group [48]; and 1 study which had the full text available only in Catalan [49]. Additionally, through a thorough examination of these articles, as well as the identified reviews and meta-analyses, we identified 5 additional resources suitable for inclusion in the present review, resulting in a final number of 64 included studies.…”

The Human Blood N-Glycome: Unraveling Disease Glycosylation Patterns

“… 60 Polymorphisms in this gene have been proposed to be implicated in attention-deficit hyperactive disorder (ADHD), albeit further evidence and validation cohorts are necessary in order to establish a causative link. 60 , 61 Intriguingly, the genetic associations of the glycome of immunoglobulin G and transferrin appeared to be divergent, reflecting the fact that those proteins are mainly B cell (plasma cell) and hepatocyte-derived, respectively. 12 This study exemplifies the power of large-scale, protein specific insights.…”

Glucosamine-loaded injectable hydrogel promotes autophagy and inhibits apoptosis after cartilage injury

“…N-acetyl- d -glucosamine (GlcNAc) is one of the three forms of glucosamine and is more stable. Studies have indicated that GlcNAc can increase proteoglycan synthesis and have anti-inflammatory properties [ 7 , 8 ].…”