Maternal plasma angiogenic and inflammatory factor profiling in foetal Down syndrome

<div><p>Objective and design</p><p>Angiogenic factors are proteins that are related to certain foetal chromosomal abnormalities. The aim of this study was to determine the concentration of 60 angiogenic factors in the plasma of women with offspring possessing trisomy 21/Down syndrome (DS).</p><p>Method</p><p>After analysing karyotyping results, we selected 20 patients with foetuses possessing DS, and for the control group, we selected 28 healthy patients with uncomplicated pregnancies who delivered healthy newborns at term (i.e., 15–18 weeks of gestation). To assess the concentration of proteins in the blood plasma, we used a protein macroarray which enabled simultaneous determination of 60 angiogenic factors per sample.</p><p>Results</p><p>We observed a statistically significant increase in the concentration of these five angiogenic and inflammatory factors: TGFb1 (p = 0.039), angiostatin (p = 0.0142), I-309 (p = 0.0476), TGFb3 (p = 0.0395), and VEGF-D (p = 0.0173)—compared to concentrations in patients with healthy foetuses.</p><p>Conclusion</p><p>Our findings suggest that angiogenic factors may play role in DS pathogenesis.</p></div

Concentrations of angiogenic factors in maternal plasma.

<p>Concentrations of angiogenic factors in maternal plasma.</p

The Effect of Acute and Chronic Social Stress on the Hippocampal Transcriptome in Mice

<div><p>Psychogenic stress contributes to the formation of brain pathology. Using gene expression microarrays, we analyzed the hippocampal transcriptome of mice subjected to acute and chronic social stress of different duration. The longest period of social stress altered the expression of the highest number of genes and most of the stress-induced changes in transcription were reversible after 5 days of rest. Chronic stress affected genes involved in the functioning of the vascular system (<i>Alas2</i>, <i>Hbb-b1</i>, <i>Hba-a2</i>, <i>Hba-a1</i>), injury response (<i>Vwf</i>, <i>Mgp</i>, <i>Cfh</i>, <i>Fbln5</i>, <i>Col3a1</i>, <i>Ctgf</i>) and inflammation (<i>S100a8</i>, <i>S100a9</i>, <i>Ctla2a</i>, <i>Ctla2b</i>, <i>Lcn2</i>, <i>Lrg1</i>, <i>Rsad2</i>, <i>Isg20</i>). The results suggest that stress may affect brain functions through the stress-induced dysfunction of the vascular system. An important issue raised in our work is also the risk of the contamination of brain tissue samples with choroid plexus. Such contamination would result in a consistent up- or down-regulation of genes, such as <i>Ttr</i>, <i>Igf2</i>, <i>Igfbp2</i>, <i>Prlr</i>, <i>Enpp2</i>, <i>Sostdc1</i>, <i>1500015O10RIK</i> (<i>Ecrg4</i>), <i>Kl</i>, <i>Clic6</i>, <i>Kcne2</i>, <i>F5</i>, <i>Slc4a5</i>, and <i>Aqp1</i>. Our study suggests that some of the previously reported, supposedly specific changes in hippocampal gene expression, may be a result of the inclusion of choroid plexus in the hippocampal samples.</p></div

Summary of microarray data.

<p>A—total number of significantly regulated genes. B—Venn diagram showing differences and similarities in gene expression between different stress regimes. Each colored ellipse represents one treatment group. Numbers of genes common between treatment groups are depicted on intersections between ellipses.</p

Expression pattern of genes assigned to clusters 2, 4–5 and 8–9.

<p>d.- days.</p

A—expression pattern of genes belonging to clusters 10. B—examples of anatomical patterns of gene expression obtained from the Allen Mouse Brain Atlas.

<p>d.- days.</p

Spearman's rank correlation between individual gene expression (PCR) and indices of stress.

<p>Correlation has been calculated for pooled data from all acute and chronic stress groups.</p><p>Spearman's rank correlation between individual gene expression (PCR) and indices of stress.</p

A—expression pattern of genes belonging to cluster 7. B—anatomical pattern of <i>Prlr</i> gene expression obtained from the Allen Mouse Brain Atlas.

<p>d.- days. Only part of the cluster is presented. For a full list of genes see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142195#pone.0142195.s003" target="_blank">S2 Table</a>.</p

The design of the experiment.

<p>Broken lines mark days when a group was not stressed. Solid lines mark days when the group was stressed. The last stress episode was performed 24 h before decapitation.</p

Quantitative qPCR validation of microarray data.

<p>Wilcoxon test, compared with corresponding control group.</p><p>Quantitative qPCR validation of microarray data.</p