The Rat Homolog of the Schizophrenia Susceptibility Gene ZNF804A Is Highly Expressed during Brain Development, Particularly in Growth Cones.

A single nucleotide polymorphism in the ZNF804A gene, rs1344706, is associated with schizophrenia. The polymorphism has been suggested to alter fetal expression of ZNF804A. It has also been reported to be associated with altered cortical functioning and neural connectivity in the brain. Since developmental mechanisms are suggested in the pathophysiology for schizophrenia, expression of Zfp804A, the rat homolog of ZNF804A, was investigated in the developing rat brain. We found that expression of Zfp804A in most brain regions is developmentally regulated and peaks around birth, where after it decreases towards adult levels. This time point is developmentally the equivalent to the second trimester of fetal development in humans. An exception to this expression pattern is the hippocampus where the expression of Zfp804A appears to increase again in the adult brain. Using laser capture and quantitative PCR we found that Zfp804A mRNA expression in the adult rat hippocampus is highest in the CA1 sub region, where the overall firing rates of neurons is higher than in the CA3 region. In cultured cortical neurons Zfp804A mRNA expression peaked at day 4 and then decreased. The ZFP804A protein expression was therefore investigated with immunochemistry in such cultures. Interestingly, before day 4, the protein is mostly found in the perinuclear region of the cell but at day 4, ZFP804A was instead found throughout the cell and particularly in the growth cones. In conclusion we demonstrate that Zfp804A increases in the rat brain at the time of birth, coinciding with neuronal differentiation. We also show that ZFP804A is localized to growth cones of growing neurites. These data implicate ZFP804A in growth cone function and neurite elongation. The polymorphism rs1344706 lowers expression of ZNF804A during prenatal brain development. This may affect ZNF804A's role in cone function and neurite elongation leading to synaptic deficits and altered neural connectivity

Health and wellbeing in refugee families from Syria resettled in Denmark

Aims: The aim was to evaluate self-reported health status and wellbeing in a well-defined group of refugee families from Syria 2–4 years after resettlement in Denmark, and, where possible, compare it with a Danish reference population. The purpose was to determine the need for specialized health care to resettled refugees. Methods: This cross-sectional study involved 90 individuals from Syria aged 13–56 years. We used questionnaire survey to assess the general health and wellbeing in the study population in relation to a Danish reference population. Objective measurements of selected health indicators like overweight, hypertension and levels of cholesterol and blood glucose (HbA1c) were also determined for the study population. Results: Mean wellbeing scores and the proportion of study participants rating their health as good were lower among the study participants compared with the Danish population for all age groups. The proportion of participants who reported often being alone against their will was significantly higher than among Danes, as was the proportion who had nobody to talk to when having problems. A significantly higher proportion of participants experienced various forms of pain or discomfort than in the Danish population. Overall, 23.6% and 3.4% of participants had elevated cholesterol and HbA1c levels, respectively, and the prevalence of overweight (BMI ≥ 25) was 70%. Hypertension was more frequent (16.2%) than in another refugee population in Denmark (9%). Conclusions: The study demonstrated various mental and physical health challenges among the Syrian refugee families, and their health and wellbeing appeared to be substantially poorer as compared to the Danish reference population. The findings emphasize the need for systematic and specialized health care services at a municipality level to resettling refugees as a prerequisite for the refugees to become contributing citizens

<i>Zfp804A</i> mRNA expression in the developing rat brain.

<p>(A) Relative <i>Zfp804A</i> mRNA expression in the frontal part of the rat cortex. <i>Zfp804A</i> expression is significantly increased at E18, P1 and P3 compared to the levels at E16 (***<i>P</i><0.001) and after P3 the level decreases significantly compared to P1 (^§§<i>P</i><0.01, ^§§§<i>P</i><0.001). (B) Relative <i>Zfp804A</i> expression in the rat cerebellum. The expression of <i>Zfp804A</i> is significantly higher at E18 and P1 compared to E16 (***<i>P</i><0.001) and lower at all time points compared to P1 (^§§§<i>P</i><0.001) except for E18. (C) Relative <i>Zfp804A</i> expression within the rat hippocampus. Expression is significantly increased in the adult rat compared to P5 (*<i>P</i><0.05). The zfp804A primer set was used and data are presented as means ± SEM. <i>Gapdh</i> was used as a reference gene and n ≥ 4</p

<i>Zfp804A</i> mRNA expression in cultured cortical neurons.

<p>The relative <i>Zfp804A</i> mRNA expression was determined in primary cortical neurons at different days <i>in-vitro</i>. The levels at day 4 were significantly increased (***<i>P</i><0.001). The zfp804A primer set was used and data is presented as means ± SEM. <i>Gapdh</i> was used as a reference gene and n ≥ 4.</p

ZFP804A is found in the cytoplasm and nucleus.

<p>Confocal ortho-images of <i>Z</i>-stacks of cultured neurons show that ZFP804A is also present in the nucleus. The center image is the <i>X-Y</i> view, the images below and right are <i>X-Z</i> and Y-Z views (cross section at the green line).</p