Joanna Rybka

Glucocorticoid-Related Molecular Signaling Pathways Regulating Hippocampal Neurogenesis

Stress and glucocorticoid hormones regulate hippocampal neurogenesis, but the molecular mechanisms underlying their effects are unknown. We, therefore, investigated the molecular signaling pathways mediating the effects of cortisol on proliferation, neuronal differentiation, and astrogliogenesis, in an immortalized human hippocampal progenitor cell line. In addition, we examined the molecular signaling pathways activated in the hippocampus of prenatally stressed rats, characterized by persistently elevated glucocorticoid levels in adulthood. In human hippocampal progenitor cells, we found that low concentrations of cortisol (100 nM) increased proliferation (+16%), decreased neurogenesis into microtubule-associated protein 2 (MAP2)-positive neurons (−24%) and doublecortin (Dcx)-positive neuroblasts (−21%), and increased differentiation into S100β-positive astrocytes (+23%). These effects were dependent on the mineralocorticoid receptor (MR) as they were abolished by the MR antagonist, spironolactone, and mimicked by the MR-agonist, aldosterone. In contrast, high concentrations of cortisol (100 μM) decreased proliferation (−17%) and neuronal differentiation into MAP2-positive neurons (−22%) and into Dcx-positive neuroblasts (−27%), without regulating astrogliogenesis. These effects were dependent on the glucocorticoid receptor (GR), blocked by the GR antagonist RU486, and mimicked by the GR-agonist, dexamethasone. Gene expression microarray and pathway analysis showed that the low concentration of cortisol enhances Notch/Hes-signaling, the high concentration inhibits TGFβ-SMAD2/3-signaling, and both concentrations inhibit Hedgehog signaling. Mechanistically, we show that reduced Hedgehog signaling indeed critically contributes to the cortisol-induced reduction in neuronal differentiation. Accordingly, TGFβ-SMAD2/3 and Hedgehog signaling were also inhibited in the hippocampus of adult prenatally stressed rats with high glucocorticoid levels. In conclusion, our data demonstrate novel molecular signaling pathways that are regulated by glucocorticoids in vitro, in human hippocampal progenitor cells, and by stress in vivo, in the rat hippocampus.

A Study of Telemedical Applications Based on User Experience

Abstract The popularity of telemedical applications has been increasing noticeably in recent years. Easy access to a variety of software products makes contemporary users concentrate not only on functionalities but also on the design of the Graphical User Interface (GUI) – its usefulness, ease of use, and intuitiveness. The objective of this study was to evaluate the GUI quality of selected telemedical applications dedicated to depressed patients and doctors providing medical care for this group of patients. Another aim of the paper was to propose and check assessment criteria applied to the evaluation experiment. To achieve this objective, the case study was based on two methods: expert analysis and cognitive walkthrough. The expert analysis study was conducted on three groups of users: user experience specialists, patients, and clinicians. Although the expert analysis method is usually dedicated to GUI design specialists, in this study, we also applied it to patient and physician groups. The results showed that there were no statistical differences between assessments carried out by those three groups of users. Applied testing criteria were revised with Nielsen’s heuristics. The proposed criteria helped to uncover many usability problems in several different areas during user tests. Further studies might be performed in order to strengthen accuracy and for completion of the proposed expert analysis evaluation criteria. However, our results show that the criteria we used seem to be robust enough to apply to both expert and end-user evaluations. Furthermore, multiple evaluation based on two different methods presented with better results, allowing not only problem identification but also verification.

Late-Life Depression and Antioxidant Supplements

Abstract Geriatric depression is a serious psychiatric condition, with a prevalence of from 10 to 40% in community-living seniors. Polymorbidity and potential vulnerability of seniors toward medication is a challenge and prompts us to seek newer, well-tolerated antidepressant-like agents and adjuvant therapies with good clinical efficiency and safety. Antioxidants targeting common pathways, and having demonstrated positive effects on many chronic diseases associated with aging, including depression, represent a promising therapeutic strategy to enhance mental health directly or indirectly. There is a substantial body of preclinical and clinical data showing positive effects of antioxidants on both the clinical symptoms of depression and the biologic processes associated with the disease. Although classic antidepressants are likely to remain a first-choice treatment in depressed patients, there is significant potential for using antioxidants as adjunct agents in elderly, depressed patients. These combinations could help to attenuate the course of the disease and its complications.