Cytokine and Chemokine Alterations in Down Syndrome

ArticleinAmerican Journal of Perinatology 29(9):705-8 · May 2012with24 Reads
DOI: 10.1055/s-0032-1314892 · Source: PubMed
Objective Down syndrome (DS) is the leading genetic cause of intellectual disability, affecting ~1/800 newborns. Previously we have shown alterations in N-methyl-D-aspartic acid (NMDA) receptors and neuropeptides (activity-dependant neuroprotective protein, glia fibrillary acidic protein) in a murine model of DS. Cytokines and chemokines have neuromodulatory and neurotransmitter roles and interact with the NMDA receptors. The objective of this study was to evaluate if cytokines and chemokines in the hippocampus and cerebellum are altered in this model. Study DesignWe used 8- to 10-month-old animals from the well-characterized mouse model of DS (Ts65Dn). Learning and memory were assessed in the Morris water maze with the Ts65Dn animals demonstrating a learning deficit. After completion of the behavioral testing, the brains were removed and the hippocampus and cerebellum were separated by microdissection. A panel of cytokines, chemokines, and fractalkine were measured in the protein lysates using a microsphere-based multiplex immunoassay (Luminex xMAP, Millipore) and normalized to total protein concentration. Statistical analysis included the nonparametric Mann-Whitney U for the cytokine, chemokine, and fractalkine levels; p<0.05 was considered significant. ResultsLevels (median [range]) of interleukin (IL)-1β (6.95 [0.11 to 43.5] versus 14.2 [0.2 to 36.8] pg/mL); granulocyte-macrophage colony-stimulating factor (GM-CSF; 3.97 [0.19 to 19.6] versus 19.2 [0.2 to 31.1] pg/mL), and macrophage inflammatory protein (MIP)-1α (20.3 [0.11 to 73.3] versus 37.0 [0.22 to 102.7] pg/mL) in the hippocampus from Ts65Dn were significantly lower compared with the euploid (control) animals. Many cytokines and chemokines were not detected in the hippocampus or cerebellum, and others were detectable but not different between the groups. Conclusion We found a decreased in GM-CSF, IL-1β, and MIP-1α in the hippocampus of DS pups. All three have known interactions with NMDA receptors and their decline may explain, in part, the learning deficits associated with DS.
  • [Show abstract] [Hide abstract] ABSTRACT: This study tests the hypothesis that pre-diagnostic serum levels of twenty cancer-associated inflammatory biomarkers correlate directly with future development of head & neck, esophageal, and lung cancers in a high-risk prospective cohort.This is a nested case-control pilot study of subjects enrolled in the Golestan Cohort Study, an ongoing epidemiologic project assessing cancer trends in Golestan, Iran. We measured a panel of 20 cytokines, chemokines, and inflammatory molecules using Luminex® technology in serum samples collected two or more years before cancer diagnosis in 78 aerodigestive cancer cases and 81 controls. Data was analyzed using Wilcoxon rank-sum test, odds ratios (OR), ROC areas of discrimination, and multivariate analysis.Biomarkers were profoundly and globally elevated in future esophageal and lung cancer patients compared to controls. Odds ratios were significant for association between several biomarkers and future development of esophageal cancer, including IL-1Rα (35.88), IFNα2 (34), FGF-2 (17.43), GM-CSF (17.43), et al. The same trend was observed among future lung cancer cases for G-CSF (27.68), GM-CSF (13.33), TNF-α (8.55), et al. By contrast, the majority of biomarkers studied showed no significant correlation with future head and neck cancer development.This study provides the first direct evidence that multiple inflammatory biomarkers are coordinately elevated in future lung and esophageal cancer patients two or more years before cancer diagnosis.This article is protected by copyright. All rights reserved.
    Full-text · Article · Jul 2014
  • [Show abstract] [Hide abstract] ABSTRACT: It is unclear whether the incidence of febrile seizure (FS) in children with Down syndrome (DS) is higher or lower than in the general population. In this study, we investigated the incidence of FS in patients with DS using mailed questionnaires. The questionnaires were distributed to parents or caregivers of patients with DS attending Osaka Medical College Hospital and six other facilities. The questionnaires were collected by mail from February 2012 to September 2013 from 323 families of patients with DS (176 were male, 147 were female; age range, 3 months to 47 years; median age, 5.0 years). To assess the incidence of FS in DS, we performed the following two analyses: (1) we calculated the incidence of FS among patients with DS between the ages of 4 and 20 years (n = 199; 113 were male, 86 were female), and (2) we extracted families with both DS and healthy siblings between the ages of 4 and 20 years (n = 150; 77 were male, 73 were female) and compared the incidence of FS in these sibling groups. Five patients with DS had a past history of FS. The incidence of FS in DS was 2.5%. The incidence of FS was significantly lower in patients with DS compared with healthy siblings (P< 0.003, Odds ratio: 0.14). Our findings suggest that the incidence of FS is lower in patients with DS than in the general population. This article is protected by copyright. All rights reserved.
    Article · Feb 2015