Signs of neurodegeneration are commonly found in schizophrenic patients, albeit still unclear, why they occur and whether they are a cause or rather an effect of schizophrenia. Although there are numerous studies supporting either theory, the working hypothesis of this thesis is that an overactivity of mesolimbic dopaminergic pathways leads to dopamine neurotoxicity in terms of an increased production of reactive oxygen species ROSin time leading to oxidative stress and thereby to so-called atypical neurodegeneration. This in turn negatively influences i. A key player in the body danger of dating a schizophrenic antioxidant capacity is the peroxisome. This cell organelle is involved in both enzymatic e. Its role danger of dating a schizophrenic schizophrenia has, however, only been poorly examined, even though peroxisomes additionally are the only known source to-date of major enzymes for the degradation of cofactors of NMDA-receptors including NMDA itself. Changes in peroxisomal metabolism and abundance therefore influence both the brain s capacity to degrade ROS as well as the functionality of its NMDA receptors and vice versa. This thesis therefore examines the reactions of peroxisomes to increased dopamine. Since peroxisomes are involved in a number of other metabolic functions apart from antioxidant defense, their enzyme content is highly heterogeneous. Catalase and ABCD3 are generally used as markers for peroxisomes. Their abundance is, however, highly dependent on metabolic demands and therefore varies extremely between as well as within different organs, tissues and cells. Especially in the brain, both catalase and ABCD3 are barely detectable, thereby leading to a marked underestimation of true peroxisomal abundance and distribution. In the first part of this thesis it was therefore attempted to establish a new peroxisomal marker, peroxin 14 Pex14pwhich is part of a docking complex on the peroxisomal membrane relevant for import of all matrix proteins and therefore independent of individual peroxisomal metabolism. Using various morphological methods in a large variety of organs, tissues and cell types from a number of different species it could be shown that Pex14p is indeed present in the membrane of every healthy peroxisome and is expressed in similarly high levels in tissue sections and cell cultures of different organs and species. As Pex14p is also highly suited as a peroxisomal marker in all neuronal tissue, post mortem brain sections of schizophrenic patients and controls were analyzed regarding the abundance and distribution of peroxisomes as well as catalase. The results were, however, inconclusive, wherefore the reactions of peroxisomes to increased dopamine were analyzed under more controllable conditions within the second part of this thesis. The effects of dopamine in vitro were examined using danger of dating a schizophrenic murine neuronal and astrocyte cell cultures and the in vivo-effects in a pharmacological mouse model through subchronic systemic administration of the selective, non-competitive NMDAR-antagonist MK Analyses of gene expression patterns from the brains of the animals show i. Danger of dating a schizophrenic experiments show that dopamine changes peroxisomal reactions and neuronal morphology specifically and only in intact neuron-astrocyte interactions, mimicking the atypical neurodegeneration found in schizophrenic patients. Additionally, increased levels of selected antioxidant enzymes were found to be increased in the brains of MKtreated animals. It can therefore be concluded that dopamine does indeed lead to increased ROS production in the brain, which is, however, initially still countered by an increase in antioxidant defense mechanisms. This strengthens the initial hypothesis that oxidative stress i. Finally, the dopamine-related increase in the expression of genes encoding for enzymes degrading NMDAR-cofactors, thereby leading to a decrease of NMDAR-mediated neurotransmission, shows that hyperdopaminergia and hypoglutamatergia in schizophrenia are not separate entities, but rather influence, uphold and even exacerbate each other. This led to the proposition of a new integrative model of the etiopathogenesis of schizophrenia, linking both hyperdopaminergia and hypoglutamatergia together. Bezüglich der bei Schizophrenen gefundenen Neurodegeneration ist die Frage nach Ursache und Wirkung unklar. Neben den Mitochondrien und dem Zytoplasma spielt das Peroxisom eine wesentliche Rolle in der enzymatischen z. Die Konzentration des klassischen peroxisomalen Markerenzyms Katalase ist jedoch in Neuronen ausgesprochen niedrig, weshalb im ersten Schritt der Arbeit ein neues Markerprotein für Peroxisomen Peroxin 14, Pex14p an einer Vielzahl verschiedener Gewebe und Zellen mittels Proteinlabelingmethoden für Elektronen- Licht- und Fluoreszenzmiskroskopie etabliert wurde. Über diese neue Methode war es nun möglich, Peroxisomen auch im Nervengewebe unabhängig ihres Katalasegehaltes zu untersuchen. Wir haben daher die Anzahl an Peroxisomen und Katalase an postmortem Hippokampusschnitten von Schizophrenen und Kontrollen verglichen. Aufgrund methodologischer Einschränkungen waren die Befunde jedoch uneindeutig. Im nächsten Schritt wurden Mischkulturen muriner Neurone und Astrozyten mit unterschiedlichen Dopaminkonzentrationen inkubiert, wonach sich eine Erhöhung der Katalasemenge vor allem in Astrozyten, begleitet von einer Umverteilung der Peroxisomen aus den Dendriten in die Somata ohne signifikante Zelltoderhöhung zeigte. Wir wiederholten diese Experimente daher mit reinen Astrozytenkulturen und fanden selbst bei Erhöhung der Dopaminkonzentration und Inkubationsdauer keine Unterschiede zu Vehikel-behandelten Kulturen. Dies spricht für die antitoxische Wirkung der Astrozyten und die Spezifität der Reaktionen aus den ersten Zellkulturen für intakte neuroastrozytäre Verbände. In darauf aufbauenden Tierversuchen untersuchten wir die Erhöhung des mesolimbischen Dopamins in männlichen Wildtypmäusen durch Gabe des NMDAR-Antagonisten MK Im Anschluss an Behandlungsdauern von 1hh wurden die Gehirne entnommen und für morphologische Analysen oder Extraktion der RNAs für Expressionsanalysen verwandt. Unsere Befunde stärken die Annahme, dass Dopamin neurodegenerative Veränderungen hervorruft und diese erst im späteren Krankheitsverlauf auftreten und daher vermutlich nicht an der Äthiopathogenese der Schizophrenie beteiligt, sondern eher als Folgeerscheinung der Dopamin-Neurotoxizität anzusehen sind. Dopamine neurotoxicity, oxidative stress and schizophrenia : in vitro and in vivo studies of peroxisomal reactions to increased dopamine. Datum Autor:innen Grant, Phillip. Weitere Beteiligte. ISSN der Zeitschrift. Lizenz In Copyright.
The development of the intervention and the program description had been published previously 1. ISSN der Zeitschrift. One hundred thirteen study participants were assessed in a cross-sectional study using a consecutive sample of patients admitted to eight acute psychiatric units and four medium secure forensic psychiatry units. Catalase and ABCD3 are generally used as markers for peroxisomes. Prevalence of depression and its relationship with other clinical characteristics in a sample of patients with stable schizophrenia.
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Positive and Negative Syndromes in schizophrenia Relationship between obsessive–compulsive symptoms and smoking habits amongst schizophrenic. Though partnerships with schizophrenia patients are at risk of breakdown and separation in many respects, they are often maintained for years. In relation to our interest to study the beginning of schizophrenia, systematically, paying special attention to the age and gender distribution of true onset. The Scale for Assessment of Negative Symptoms (SANS) (31) measures schizophrenia's deficit symptoms within the framework of schizophrenic. Despite the.Each participant gave his written informed consent to participate in this study. These findings reveal an important target for interventions to improve the TR: Psychopharmacological options as well as communicative strategies e. The scales of the SANS were divided into a composite score of the reduction of the ability to experience and a composite score of the reduction of expression. Coercive measures in psychiatry are assumed to handicap, or even worse to erode, the TR [ 12 ]. PubMedPubMedCentralCrossRef Zhang Y. Review of clinical characteristics and mortality outcomes in patients on maintenance hemodialysis during the Omicron surge: a single center experience Open Access Research. PubMedCrossRef Zung WW. The results showed that sex, total and type of psychiatric medication, number of outpatient follow-up visits, history of hospitalization for mental disorders and sleep disturbance were all influencing factors for the occurrence of aggressive behaviour among the surveyed subjects. Zurück zum Zitat Wang Z, Chen M, Wei YZ, Zhuo CG, Xu HF, Li WD, Ma L. Ethical approval was granted by the Kantonale Ethikkommission Zürich, Switzerland no. Furthermore, no agreement in judgments of the quality of the TR between the ratings of patients and physicians could be observed. A Spanish version of the Three-Dimensional Work Fatigue Inventory 3D-WFI : factor structure, internal consistency, and criterion validity Open Access Research. Reduced frontostriatal functional connectivity associated with negative symptoms might provide a supplementary hypothesis to study the neurobiological mechanisms of negative symptoms Wir haben daher die Anzahl an Peroxisomen und Katalase an postmortem Hippokampusschnitten von Schizophrenen und Kontrollen verglichen. CrossRef El-Sheikh M, Buckhalt JA, Mark Cummings E, Keller P. At the same time, family members should be guided to provide sufficient care to patients with schizophrenia, understand their true thoughts in a timely manner, and create a warm, safe, and loving family. Int J Environ Res Public Health 3. J Clin Nurs. PubMedCrossRef Yang CR, Bai YY, Ruan CS, Zhou HF, Liu D, Wang XF, Shen LJ, Zheng HY, Zhou XF. Search PMC Full-Text Archive Search in PMC Advanced Search Journal List User Guide. We found that neither legal detention nor the presence of psychotic symptoms in general was associated with the ratings of the TR. Second, this study adopted a cross-sectional design, and although it identified risk factors for aggressive behaviour among community schizophrenia patients, there were no causal conclusions. All patients received a complete clinical psychiatric evaluation based on the Structured Clinical Interview for DSM-IV The results of this study showed that patients with schizophrenia exhibited aggressive behaviour, accounting for Add to Collections. The perceived burden among Chinese family caregivers of people with schizophrenia. PubMedCrossRef Olson DH, Russell CS, Sprenkle DH. Forensic psychiatric patients, on average, gave an intermediate rating of the quality of the therapeutic relationship.
