@article{StetterLopezCaperuchipiHoppKraemeretal.2021, author = {Stetter, Christian and Lopez-Caperuchipi, Simon and Hopp-Kr{\"a}mer, Sarah and Bieber, Michael and Kleinschnitz, Christoph and Sir{\´e}n, Anna-Leena and Albert-Weißenberger, Christiane}, title = {Amelioration of cognitive and behavioral deficits after traumatic brain injury in coagulation factor XII deficient mice}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {9}, issn = {1422-0067}, doi = {10.3390/ijms22094855}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284959}, year = {2021}, abstract = {Based on recent findings that show that depletion of factor XII (FXII) leads to better posttraumatic neurological recovery, we studied the effect of FXII-deficiency on post-traumatic cognitive and behavioral outcomes in female and male mice. In agreement with our previous findings, neurological deficits on day 7 after weight-drop traumatic brain injury (TBI) were significantly reduced in FXII\(^{-/-}\) mice compared to wild type (WT) mice. Also, glycoprotein Ib (GPIb)-positive platelet aggregates were more frequent in brain microvasculature of WT than FXII\(^{-/-}\) mice 3 months after TBI. Six weeks after TBI, memory for novel object was significantly reduced in both female and male WT but not in FXII\(^{-/-}\) mice compared to sham-operated mice. In the setting of automated home-cage monitoring of socially housed mice in IntelliCages, female WT mice but not FXII\(^{-/-}\) mice showed decreased exploration and reacted negatively to reward extinction one month after TBI. Since neuroendocrine stress after TBI might contribute to trauma-induced cognitive dysfunction and negative emotional contrast reactions, we measured peripheral corticosterone levels and the ration of heart, lung, and spleen weight to bodyweight. Three months after TBI, plasma corticosterone levels were significantly suppressed in both female and male WT but not in FXII\(^{-/-}\) mice, while the relative heart weight increased in males but not in females of both phenotypes when compared to sham-operated mice. Our results indicate that FXII deficiency is associated with efficient post-traumatic behavioral and neuroendocrine recovery.}, language = {en} } @article{SchleeSimoesPryss2021, author = {Schlee, Winfried and Simoes, Jorge and Pryss, R{\"u}diger}, title = {Auricular acupressure combined with self-help intervention for treating chronic tinnitus: a longitudinal observational study}, series = {Journal of Clinical Medicine}, volume = {10}, journal = {Journal of Clinical Medicine}, number = {18}, issn = {2077-0383}, doi = {10.3390/jcm10184201}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246209}, year = {2021}, abstract = {Tinnitus is a phantom sound perception in the ears or head and can arise from many different medical disorders. Currently, there is no standard treatment for tinnitus that reliably reduces tinnitus. Individual patients reported that acupressure at various points around the ear can help to reduce tinnitus, which was investigated here. With this longitudinal observational study, we report a systematic evaluation of auricular acupressure on 39 tinnitus sufferers, combined with a self-help smartphone app. The participants were asked to report on tinnitus, stress, mood, neck, and jaw muscle tensions twice a day using an ecological momentary assessment study design for six weeks. On average, 123.6 questionnaires per person were provided and used for statistical analysis. The treatment responses of the participants were heterogeneous. On average, we observed significant negative trends for tinnitus loudness (Cohen's d effect size: -0.861), tinnitus distress (d = -0.478), stress (d = -0.675), and tensions in the neck muscles (d = -0.356). Comparison with a matched control group revealed significant improvements for tinnitus loudness (p = 0.027) and self-reported stress level (p = 0.003). The positive results of the observational study motivate further research including a randomized clinical trial and long-term assessment of the clinical improvement.}, language = {en} } @article{PishvaDrukkerViechtbaueretal.2014, author = {Pishva, Ehsan and Drukker, Marjan and Viechtbauer, Wolfgang and Decoster, Jeroen and Collip, Dina and van Winkel, Ruud and Wichers, Marieke and Jacobs, Nele and Thiery, Evert and Derom, Catherine and Geschwind, Nicole and van den Hove, Daniel and Lataster, Tineke and Myin-Germeys, Inez and van Os, Jim and Rutten, Bart P. F. and Kenis, Gunter}, title = {Epigenetic Genes and Emotional Reactivity to Daily Life Events: A Multi-Step Gene-Environment Interaction Study}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {6}, issn = {1932-6203}, doi = {10.1371/journal.pone.0100935}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115956}, pages = {e100935}, year = {2014}, abstract = {Recent human and animal studies suggest that epigenetic mechanisms mediate the impact of environment on development of mental disorders. Therefore, we hypothesized that polymorphisms in epigenetic-regulatory genes impact stress-induced emotional changes. A multi-step, multi-sample gene-environment interaction analysis was conducted to test whether 31 single nucleotide polymorphisms (SNPs) in epigenetic-regulatory genes, i.e. three DNA methyltransferase genes DNMT1, DNMT3A, DNMT3B, and methylenetetrahydrofolate reductase (MTHFR), moderate emotional responses to stressful and pleasant stimuli in daily life as measured by Experience Sampling Methodology (ESM). In the first step, main and interactive effects were tested in a sample of 112 healthy individuals. Significant associations in this discovery sample were then investigated in a population-based sample of 434 individuals for replication. SNPs showing significant effects in both the discovery and replication samples were subsequently tested in three other samples of: (i) 85 unaffected siblings of patients with psychosis, (ii) 110 patients with psychotic disorders, and iii) 126 patients with a history of major depressive disorder. Multilevel linear regression analyses showed no significant association between SNPs and negative affect or positive affect. No SNPs moderated the effect of pleasant stimuli on positive affect. Three SNPs of DNMT3A (rs11683424, rs1465764, rs1465825) and 1 SNP of MTHFR (rs1801131) moderated the effect of stressful events on negative affect. Only rs11683424 of DNMT3A showed consistent directions of effect in the majority of the 5 samples. These data provide the first evidence that emotional responses to daily life stressors may be moderated by genetic variation in the genes involved in the epigenetic machinery.}, language = {en} } @article{WaiderPoppLangeetal.2017, author = {Waider, J and Popp, S and Lange, MD and Kern, R and Kolter, JF and Kobler, J and Donner, NC and Lowe, KR and Malzbender, JH and Brazell, CJ and Arnold, MR and Aboagye, B and Schmitt-B{\"o}hrer, A and Lowry, CA and Pape, HC and Lesch, KP}, title = {Genetically driven brain serotonin deficiency facilitates panic-like escape behavior in mice}, series = {Translational Psychiatry}, volume = {7}, journal = {Translational Psychiatry}, number = {e1246}, doi = {10.1038/tp.2017.209}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170239}, year = {2017}, abstract = {Multiple lines of evidence implicate brain serotonin (5-hydroxytryptamine; 5-HT) system dysfunction in the pathophysiology of stressor-related and anxiety disorders. Here we investigate the influence of constitutively deficient 5-HT synthesis on stressor-related anxiety-like behaviors using Tryptophan hydroxylase 2 (Tph2) mutant mice. Functional assessment of c-Fos after associated foot shock, electrophysiological recordings of GABAergic synaptic transmission, differential expression of the Slc6a4 gene in serotonergic neurons were combined with locomotor and anxiety-like measurements in different contextual settings. Our findings indicate that constitutive Tph2 inactivation and consequential lack of 5-HT synthesis in Tph2 null mutant mice (Tph2\(^{-/-}\)) results in increased freezing to associated foot shock and a differential c-Fos activity pattern in the basolateral complex of the amygdala. This is accompanied by altered GABAergic transmission as observed by recordings of inhibitory postsynaptic currents on principal neurons in the basolateral nucleus, which may explain increased fear associated with hyperlocomotion and escape-like responses in aversive inescapable contexts. In contrast, lifelong 5-HT deficiency as observed in Tph2 heterozygous mice (Tph\(^{+/-}\)) is able to be compensated through reduced GABAergic transmission in the basolateral nucleus of the amygdala based on Slc6a4 mRNA upregulation in subdivisions of dorsal raphe neurons. This results in increased activity of the basolateral nucleus of the amygdala due to associated foot shock. In conclusion, our results reflect characteristic syndromal dimensions of panic disorder and agoraphobia. Thus, constitutive lack of 5-HT synthesis influence the risk for anxiety- and stressor-related disorders including panic disorder and comorbid agoraphobia through the absence of GABAergic-dependent compensatory mechanisms in the basolateral nucleus of the amygdala.}, language = {en} } @article{KastenNaserBruellhoffetal.2014, author = {Kasten, Annika and Naser, Tamara and Br{\"u}llhoff, Kristina and Fiedler, J{\"o}rg and M{\"u}ller, Petra and M{\"o}ller, Martin and Rychly, Joachim and Groll, J{\"u}rgen and Brenner, Rolf E.}, title = {Guidance of Mesenchymal Stem Cells on Fibronectin Structured Hydrogel Films}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {10}, doi = {10.1371/journal.pone.0109411}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114897}, pages = {e109411}, year = {2014}, abstract = {Designing of implant surfaces using a suitable ligand for cell adhesion to stimulate specific biological responses of stem cells will boost the application of regenerative implants. For example, materials that facilitate rapid and guided migration of stem cells would promote tissue regeneration. When seeded on fibronectin (FN) that was homogeneously immmobilized to NCO-sP(EO-stat-PO), which otherwise prevents protein binding and cell adhesion, human mesenchymal stem cells (MSC) revealed a faster migration, increased spreading and a more rapid organization of different cellular components for cell adhesion on fibronectin than on a glass surface. To further explore, how a structural organization of FN controls the behavior of MSC, adhesive lines of FN with varying width between 10 mu m and 80 mu m and spacings between 5 mu m and 20 mu m that did not allow cell adhesion were generated. In dependance on both line width and gaps, cells formed adjacent cell contacts, were individually organized in lines, or bridged the lines. With decreasing sizes of FN lines, speed and directionality of cell migration increased, which correlated with organization of the actin cytoskeleton, size and shape of the nuclei as well as of focal adhesions. Together, defined FN lines and gaps enabled a fine tuning of the structural organization of cellular components and migration. Microstructured adhesive substrates can mimic the extracellular matrix in vivo and stimulate cellular mechanisms which play a role in tissue regeneration.}, language = {en} } @article{WeberLorenzHemmings2019, author = {Weber, Silvana and Lorenz, Christopher and Hemmings, Nicola}, title = {Improving stress and positive mental health at work via an app-based intervention: a large-scale multi-center randomized control trial}, series = {Frontiers in Psychology}, volume = {10}, journal = {Frontiers in Psychology}, number = {2745}, issn = {1664-1078}, doi = {10.3389/fpsyg.2019.02745}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194337}, year = {2019}, abstract = {Mobile health interventions (i.e., "apps") are used to address mental health and are an increasingly popular method available to both individuals and organizations to manage workplace stress. However, at present, there is a lack of research on the effectiveness of mobile health interventions in counteracting or improving stress-related health problems, particularly in naturalistic, non-clinical settings. This project aimed at validating a mobile health intervention (which is theoretically grounded in the Job Demands-Resources Model) in preventing and managing stress at work. Within the mobile health intervention, employees make an evidence-based, personalized, psycho-educational journey to build further resources, and thus, reduce stress. A large-scale longitudinal randomized control trial, conducted with six European companies over 6 weeks using four measurement points, examined indicators of mental health via measures of stress, wellbeing, resilience, and sleep. The data were analyzed by means of hierarchical multilevel models for repeated measures, including both self-report measures and user behavior metrics from the app. The results (n = 532) suggest that using the mobile health intervention (vs. waitlist control group) significantly improved stress and wellbeing over time. Higher engagement in the intervention increased the beneficial effects. Additionally, use of the sleep tracking function led to an improvement in sleeping troubles. The intervention had no effects on measures of physical health or social community at work. Theoretical and practical implications of these findings are discussed, focusing on benefits and challenges of using technological solutions for organizations to support individuals' mental health in the workplace.}, language = {en} } @article{ScheinerDaunkeSeideletal.2023, author = {Scheiner, Christin and Daunke, Andrea and Seidel, Alexandra and Mittermeier, Sabrina and Romanos, Marcel and K{\"o}lch, Michael and Buerger, Arne}, title = {LessStress - how to reduce stress in school: evaluation of a universal stress prevention in schools: study protocol of a cluster-randomised controlled trial}, series = {Trials}, volume = {24}, journal = {Trials}, number = {1}, doi = {10.1186/s13063-022-06970-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300393}, year = {2023}, abstract = {Background Chronic stress is detrimental to health, and children and young people have had to cope with significantly more stress since the start of the COVID-19 pandemic. In particular, stress at school and in relation to learning is a major problem in this age group. Studies in Germany have indicated that the pandemic has led to a reduced quality of life (QoL) and an increased risk for psychiatric disorders in children and adolescents. Schools are an ideal setting for interventions against stress, which is one of the strongest predictors for the development of psychosocial problems. The present study seeks to address stress by means of a short prevention training programme in schools, including emotion regulation, mindfulness, and self-compassion. In addition to information material for self-study, students should have the opportunity to actively deal with the topic of stress and develop coping strategies within a short space of time. In contrast to very long stress reduction programmes that often last several weeks, the programme is delivered in just 90 min. Methods The effectiveness of the short and economical prevention programme LessStress will be examined in a cluster-randomised controlled trial (RCT) encompassing 1894 students. At several measurement time points, students from two groups (intervention and control) will be asked about their subjectively perceived stress levels, among other aspects. Due to the clustered nature of the data, mainly multilevel analyses will be performed. Discussion In Germany, there are no nationwide universal prevention programmes for students against stress in schools, and this gap has become more evident since the outbreak of the pandemic. Universal stress prevention in schools may be a starting point to promote resilience. By dealing with stress in a healthy way, mental health can be strengthened and maintained. Moreover, to reach at-risk students at an early stage, we advocate for a stronger networking between child psychiatry and schools.}, language = {en} } @article{LeonhardtWinklerKollikowskietal.2023, author = {Leonhardt, Jonas and Winkler, Marcela and Kollikowski, Anne and Schiffmann, Lisa and Quenzer, Anne and Einsele, Hermann and L{\"o}ffler, Claudia}, title = {Mind-body-medicine in oncology—from patient needs to tailored programs and interventions}, series = {Frontiers in Psychology}, volume = {14}, journal = {Frontiers in Psychology}, issn = {1664-1078}, doi = {10.3389/fpsyg.2023.1140693}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321970}, year = {2023}, abstract = {Introduction: National and international guidelines recommend early integration of evidence-based multimodal interventions and programs, especially with a focus on relaxation techniques and other Mind-Body-based methods to maintain the quality of life of oncology patients, improve treatment tolerability, and promote healthy lifestyle behaviors. Consequently, we aim to understand what drives patients and how they navigate integrative medicine to best advise them. This study aimed to detect possible topics of particular interest to patients and identify the patient groups that could benefit most from further programs. Furthermore, we aimed to investigate if patients are open-minded toward integrative oncology concepts and learn about their motivational level to maintain or change behavior. Methods: Between August 2019 and October 2020 we surveyed patients undergoing oncological therapy in a university oncological outpatient center using a custom-developed questionnaire based on established Mind-Body Medicine concepts. Results: We included 294 patients with various cancers. More than half reported problems sleeping through (61\%) and 42\% felt stressed frequently, invariably rating this as detrimental to their health. Moreover, a slight majority (52\%) felt physically limited due to their disease and only 30\% performed defined exercise programs. Women were significantly more likely to feel stressed and reported with alarming frequency that they often feel "everything was up to them." The 40-65-year-olds reported significantly less restful sleep, more stress and were more dissatisfied with their situation. However, this group already used natural remedies most frequently and was most often motivated to use relaxation techniques in the next 6 months. The lower the perceived individual energy level (EL), the less frequently patients did sport, the more frequently they felt their disease impaired their activity, mostly feeling stressed and tense. We also found significant associations between negative emotions/thoughts and the variables "sleep," "use of relaxation techniques," "personal stress perception," and "successful lifestyle modification." Conclusion: Mind-Body programs that focus on patient's individual resources, with tools to explore impairing patterns of self-perception and cognitive biases, can be a valuable resource for oncology patients and should therefore be part of an integrative medical treatment concept.}, language = {en} } @article{MurakawaHinzMothesetal.2015, author = {Murakawa, Yasuhiro and Hinz, Michael and Mothes, Janina and Schuetz, Anja and Uhl, Michael and Wyler, Emanuel and Yasuda, Tomoharu and Mastrobuoni, Guido and Friedel, Caroline C. and D{\"o}lken, Lars and Kempa, Stefan and Schmidt-Supprian, Marc and Bl{\"u}thgen, Nils and Backofen, Rolf and Heinemann, Udo and Wolf, Jana and Scheidereit, Claus and Landthaler, Markus}, title = {RC3H1 post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-\(\kappa\)B pathway}, series = {Nature Communications}, volume = {6}, journal = {Nature Communications}, number = {7367}, doi = {10.1038/ncomms8367}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151596}, year = {2015}, abstract = {The RNA-binding protein RC3H1 (also known as ROQUIN) promotes TNF\(\alpha\) mRNA decay via a 3'UTR constitutive decay element (CDE). Here we applied PAR-CLIP to human RC3H1 to identify ~3,800 mRNA targets with >16,000 binding sites. A large number of sites are distinct from the consensus CDE and revealed a structure-sequence motif with U-rich sequences embedded in hairpins. RC3H1 binds preferentially short-lived and DNA damage-induced mRNAs, indicating a role of this RNA-binding protein in the post-transcriptional regulation of the DNA damage response. Intriguingly, RC3H1 affects expression of the NF-\(\kappa\)B pathway regulators such as I\(\kappa\)B\(\alpha\) and A20. RC3H1 uses ROQ and Zn-finger domains to contact a binding site in the A20 3'UTR, demonstrating a not yet recognized mode of RC3H1 binding. Knockdown of RC3H1 resulted in increased A20 protein expression, thereby interfering with I\(\kappa\)B kinase and NF-\(\kappa\)B activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-\(\kappa\)B pathway.}, language = {en} } @article{NowackaChmielewskaGrabowskaGrabowskietal.2022, author = {Nowacka-Chmielewska, Marta and Grabowska, Konstancja and Grabowski, Mateusz and Meybohm, Patrick and Burek, Malgorzata and Małecki, Andrzej}, title = {Running from stress: neurobiological mechanisms of exercise-induced stress resilience}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {21}, issn = {1422-0067}, doi = {10.3390/ijms232113348}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297407}, year = {2022}, abstract = {Chronic stress, even stress of a moderate intensity related to daily life, is widely acknowledged to be a predisposing or precipitating factor in neuropsychiatric diseases. There is a clear relationship between disturbances induced by stressful stimuli, especially long-lasting stimuli, and cognitive deficits in rodent models of affective disorders. Regular physical activity has a positive effect on the central nervous system (CNS) functions, contributes to an improvement in mood and of cognitive abilities (including memory and learning), and is correlated with an increase in the expression of the neurotrophic factors and markers of synaptic plasticity as well as a reduction in the inflammatory factors. Studies published so far show that the energy challenge caused by physical exercise can affect the CNS by improving cellular bioenergetics, stimulating the processes responsible for the removal of damaged organelles and molecules, and attenuating inflammation processes. Regular physical activity brings another important benefit: increased stress robustness. The evidence from animal studies is that a sedentary lifestyle is associated with stress vulnerability, whereas a physically active lifestyle is associated with stress resilience. Here, we have performed a comprehensive PubMed Search Strategy for accomplishing an exhaustive literature review. In this review, we discuss the findings from experimental studies on the molecular and neurobiological mechanisms underlying the impact of exercise on brain resilience. A thorough understanding of the mechanisms underlying the neuroprotective potential of preconditioning exercise and of the role of exercise in stress resilience, among other things, may open further options for prevention and therapy in the treatment of CNS diseases.}, language = {en} }