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Quantitative proteomic analyses of cerebrospinal fluid using iTRAQ in a primate model of iron deficiency anemia.

ABSTRACT: Iron deficiency affects nearly 2 billion people worldwide, with pregnant women and young children being most severely impacted. Sustained anemia during the first year of life can cause cognitive, attention and motor deficits, which may persist despite iron supplementation. We conducted iTRAQ analyses on cerebrospinal fluid (CSF) from infant monkeys (Macaca mulatta) to identify differential protein expression associated with early iron deficiency. CSF was collected from 5 iron-sufficient and 8 iron-deficient anemic monkeys at weaning age (6-7 months) and again at 12-14 months. Despite consumption of iron-fortified food after weaning, which restored hematological indices into the normal range, expression of 5 proteins in the CSF remained altered. Most of the proteins identified are involved in neurite outgrowth, migration or synapse formation. The results reveal novel ways in which iron deficiency undermines brain growth and results in aberrant neuronal migration and connections. Taken together with gene expression data from rodent models of iron deficiency, we conclude that significant alterations in neuroconnectivity occur in the iron-deficient brain, which may persist even after resolution of the hematological anemia. The compromised brain infrastructure could account for observations of behavioral deficits in children during and after the period of anemia.

SUBMITTER: Patton SM

PROVIDER: S-EPMC4373703 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Quantitative proteomic analyses of cerebrospinal fluid using iTRAQ in a primate model of iron deficiency anemia.

Patton Stephanie M SM Coe Christopher L CL Lubach Gabriele R GR Connor James R JR

Developmental neuroscience 20120926 4

Iron deficiency affects nearly 2 billion people worldwide, with pregnant women and young children being most severely impacted. Sustained anemia during the first year of life can cause cognitive, attention and motor deficits, which may persist despite iron supplementation. We conducted iTRAQ analyses on cerebrospinal fluid (CSF) from infant monkeys (Macaca mulatta) to identify differential protein expression associated with early iron deficiency. CSF was collected from 5 iron-sufficient and 8 ir ...[more]

PMID: 23018452

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Project description:The diagnosis of multiple sclerosis (MS) is challenging for the lack of a specific diagnostic test. Recent researches in quantitative proteomics, however, offer new opportunities for biomarker discovery and the study of disease pathogenesis. To find more potential protein biomarkers, we used two technologies, 2-dimensional fluorescence difference in-gel electrophoresis (2D-DIGE), followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and ultra-performance liquid chromato-graph coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS), to quantitatively analyse differential proteomic expression in the cerebrospinal fluid (CSF) between patients with MS (the experiment group) and patients with other neurological diseases (ONDs; the control group). Analysis by the former technology identified more than 43 different protein spots (39 proteins), of which 17 spots (13 proteins) showed more than 1.5-fold difference in abundance as analysed by DeCyder software (GE Healthcare, Piscataway. NJ, USA) between the MS and the ONDs groups. The expression of five protein spots was elevated and the expression of 12 protein spots was decreased in the MS group. Meanwhile, the latter method, UPLC/Q-TOF MS showed 68 different proteins. There were 45 proteins with a difference of more than 1.5 folds between the two groups, in which the expression of 20 proteins was elevated and the expression of 25 proteins was decreased in the MS group. Data provided by the two methods indicated that the proteins overlapped ratio was 27% in the 26 significant proteins that had the same regulation tendency. The differential CSF proteins were analysed further by biological network and it revealed interaction of them. The subsequent ELISA measuring the concentration of cystatin C (P < 0.01), which was one of the proteins discovered simultaneously with the two technologies, confirmed the results of the two quantitative proteomic analysis. The combination of the two quantitative proteomic technologies was helpful in discovering differentially expressed proteins that may have a connection with MS disease physiology and serve as useful biomarkers for diagnosis and treatment of MS diseases.

Dataset Information

Quantitative proteomic analyses of cerebrospinal fluid using iTRAQ in a primate model of iron deficiency anemia.

Publications

Quantitative proteomic analyses of cerebrospinal fluid using iTRAQ in a primate model of iron deficiency anemia.

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