Human in vitro reporter model of neuronal development and early differentiation processes

<p>Abstract</p> <p>Background</p> <p>During developmental and adult neurogenesis, doublecortin is an early neuronal marker expressed when neural stem cells assume a neuronal cell fate. To understand mechanisms involved in early processes of neuronal fate decision, we investigated cell lines for their capacity to induce expression of doublecortin upon neuronal differentiation and develop <it>in vitro </it>reporter models using doublecortin promoter sequences.</p> <p>Results</p> <p>Among various cell lines investigated, the human teratocarcinoma cell line NTERA-2 was found to fulfill our criteria. Following induction of differentiation using retinoic acid treatment, we observed a 16-fold increase in doublecortin mRNA expression, as well as strong induction of doublecortin polypeptide expression. The acquisition of a neuronal precursor phenotype was also substantiated by the establishment of a multipolar neuronal morphology and expression of additional neuronal markers, such as Map2, βIII-tubulin and neuron-specific enolase. Moreover, stable transfection in NTERA-2 cells of reporter constructs encoding fluorescent or luminescent genes under the control of the doublecortin promoter allowed us to directly detect induction of neuronal differentiation in cell culture, such as following retinoic acid treatment or mouse Ngn2 transient overexpression.</p> <p>Conclusion</p> <p>Induction of doublecortin expression in differentiating NTERA-2 cells suggests that these cells accurately recapitulate some of the very early events of neuronal determination. Hence, the use of reporter genes under the control of the doublecortin promoter in NTERA-2 cells will help us to investigate factors involved early in the course of neuronal differentiation processes. Moreover the ease to detect the induction of a neuronal program in this model will permit to perform high throughput screening for compounds acting on the early neuronal differentiation mechanisms.</p

Healthy dietary indices and risk of depressive outcomes : a systematic review and meta-analysis of observational studies

With depression being the psychiatric disorder incurring the largest societal costs in developed countries, there is a need to gather evidence on the role of nutrition in depression, to help develop recommendations and guide future psychiatric health care. The aim of this systematic review was to synthesize the link between diet quality, measured using a range of predefined indices, and depressive outcomes. Medline, Embase and PsychInfo were searched up to 31st May 2018 for studies that examined adherence to a healthy diet in relation to depressive symptoms or clinical depression. Where possible, estimates were pooled using random effect meta-analysis with stratification by observational study design and dietary score. A total of 20 longitudinal and 21 cross-sectional studies were included. These studies utilized an array of dietary measures, including: different measures of adherence to the Mediterranean diet, the Healthy Eating Index (HEI) and Alternative HEI (AHEI), the Dietary Approaches to Stop Hypertension, and the Dietary Inflammatory Index. The most compelling evidence was found for the Mediterranean diet and incident depression, with a combined relative risk estimate of highest vs. lowest adherence category from four longitudinal studies of 0.67 (95% CI 0.55-0.82). A lower Dietary Inflammatory Index was also associated with lower depression incidence in four longitudinal studies (relative risk 0.76; 95% CI: 0.63-0.92). There were fewer longitudinal studies using other indices, but they and cross-sectional evidence also suggest an inverse association between healthy diet and depression (e.g., relative risk 0.65; 95% CI 0.50-0.84 for HEI/AHEI). To conclude, adhering to a healthy diet, in particular a traditional Mediterranean diet, or avoiding a pro-inflammatory diet appears to confer some protection against depression in observational studies. This provides a reasonable evidence base to assess the role of dietary interventions to prevent depression.Peer reviewe

Nocturnal Traffic Noise and Morning Cognitive Performance

Introduction: Exposure to traffic noise during nighttime is a growing problem. Annoyance and complaints about disturbed sleep are steadily increasing and hence call for noise protection. This study focused on the impact of nocturnal noise exposure to air, road, and rail traffic on sleep and performance. Methods: 72 subjects (40 ± 13 years, 32 male) were polysomnographically examined during 11 consecutive nights. A psychomotor vigilance task (PVT), a memory search task and an unstable tracking task were conducted after waking up in the morning. Traffic noise was played back in the laboratory during the night with 8 h time in bed. Each traffic mode consisted of five noise categories (maximum sound pressure level 45, 50, 55, 60 and 65 dBA) with 8 different noise events, i.e. 40 noise events in total. Therefore, between 40 and 120 noise events were realistically played back during single (AI, RO, RA, RORO), double (AIRO, AIRA, RORA) and triple (AIRORA) exposure nights. The design was complemented with a noise-free control night and carefully balanced. Mixed model ANOVA was used for statistical analyses. Results: Only mean reaction time in PVT increased significantly by 3.6 ms (± 1.3 ms SE, p = 0.0069) after exposure nights. Reaction time increased significantly both with an increasing number of noise events (between 4.5 and 4.9 ms) and with equivalent noise level LAS,eq (between 4.8 and 5.0 ms) compared to the control night. Different traffic modes, or single compared to combined exposure nights, did not lead to specific performance alterations. Furthermore, combined traffic noise exposure conditions did not lead to stronger performance impairments than the single exposure conditions; effects were less than additive. Conclusions: Sleep disruptions caused by different traffic modes seem to be uniform in the resulting performance decrements on the following day. Conflict of Interest: The authors declare that they have no conflict of interest