Migrationsanalysen an den humanen Glioblastomzelllinien U-373 MG und U-87 MG unter Anwendung von Medikamenten des klinischen Alltags

Das Glioblastoma multiforme ist einer der häufigsten hirneigenen Tumoren des Menschen und die Prognose für die daran erkrankten Patienten trotz multidisziplinärer Therapieschemata noch immer infaust. Insofern verwundert es kaum, dass diese Tumorentität unter anderem in der experimentellen Forschung in Bezug auf die molekularen Stoffwechselmechanismen und die Interaktion der Zellen mit der Umwelt weit verbreitet ist. Und obwohl immer mehr dieser Signalwege entschlüsselt werden, hat sich bis jetzt noch kein bahnbrechender Therapieansatz offenbart. Gegenstand dieser Arbeit ist es, die Wirkung von Medikamenten der alltäglichen, klinischen Praxis auf die Migrationsrate kultivierter humaner Glioblastomzellen zu untersuchen. Hintergrund dessen ist vor allem die Erkenntnis, dass infolge der malignen Tumorbiologie des Zellverbandes in vivo eine Störung der Blut-Hirn-Schranke resultiert (Long 1970), sodass letztlich jedes systemisch verabreichte Medikament auf sie einwirken kann. Daher wurde ein breites Spektrum häufig angeordneter Wirkstoffe in ihrer handelsüblichen Zubereitungsform (für die intravenöse Gabe) ausgewählt, auch im Hinblick auf eine ähnliche Studie über eine intrazelluläre Kalziumantwort unter einer erstaunlichen Vielzahl solcher Medikamente (Kuhn et al. 2009). Diese wurden Glioblastomzellen der Linien U-373 MG und U-87 MG in verschiedenen Konzentrationen zugesetzt und deren Migrationsrate in drei unterschiedlichen Transwell-Verfahren erfasst. Die statistische Auswertung der damit erhobenen Ergebnisse kann mit multiplen signifikanten Effekten der Medikamente auf die Wanderungsbestrebungen der beiden Zelllinien aufwarten. (…

Hippocampal volume as a putative marker of resilience or compensation to minor depressive symptoms in a nonclinical sample

Case-control studies in major depression have established patterns of regional gray matter loss, including the hippocampus, which might show state-related effects dependent on disease stage. However, there is still limited knowledge on compensation effects that might occur in people resilient to depression showing only subclinical symptoms. We used voxel-based morphometry on a multicenter data set of 409 healthy nonclinical subjects to test the hypothesis that local hippocampal volume would be inversely correlated with subclinical depressive symptoms [Symptom Checklist 90-Revised (SCL-90-R) depression scores]. Our region-of-interest results show a significant (p = 0.042, FWE cluster-level corrected) positive correlation of SCL-90-R scores for depression and a left hippocampus cluster. Additionally, we provide an exploratory finding of gyrification, a surface-based morphometric marker, correlating with a right postcentral gyrus cluster [p = 0.031, family-wise error (FWE) cluster-level corrected]. Our findings provide first preliminary evidence of an inverse relationship for subjects in the absence of clinical depression and might thus point to processes related to compensation. Similar effects have been observed in remission from major depression and thus deserve further study to evaluate hippocampal volume not only as a state-dependent marker of disease but also of resilience

Human time perspective and its structural associations with voxel-based morphometry and gyrification

Time perspective refers to humans' concept of integrating and evaluating temporal position and evaluation of memories, emotions, and experiences. We tested the hypothesis that different aspects of time perspective, as assessed with the Zimbardo Time Perspective Inventory (ZTPI) are related to variation of brain structure in non-clinical subjects. Analysing data from n = 177 psychiatrically healthy subjects using voxel-based morphometry with the CAT12 software package, we identified several significant (p < 0.05 FWE, cluster-level corrected) associations. The factors past negative, reflecting a negative attitude towards past events and present fatalistic, measuring a hopeless and fatalistic attitude towards future life, were both negatively associated with grey matter volumes of the anterior insula. The ZTPI factor future was negatively associated with precuneus grey matter. There was no association of ZTPI scores with gyrification using an absolute mean curvature method, a marker of early brain development. These findings provide a link between a general psychological construct of time perspective and brain structural variations in key areas related to time keeping (anterior insula) and the default mode network (precuneus), both of which overlap with variation in behavioral aspects and psychopathology

Brain structural correlates of irritability: findings in a large healthy cohort

Irritability and nonviolent aggression are common behavioral features across the population, yet there is limited neurobiological research into subclinical phenotypes representing the lower edge of a symptom continuum ranging from slight irritability to criminal violence. We studied brain structural correlates of irritability in a large healthy cohort to test the hypothesis of associations with fronto-limbic brain structures implicated in mood regulation. In a large multicenter effort, we recruited 409 mentally healthy adults from the community, who received T1-weighted high-resolution 3\ua0T MRI scans. These structural scans were automatically preprocessed for voxel- and surface-based morphometry measurements with the CAT 12 toolbox implemented in SPM 12. Subclinical aggressive symptoms were assessed using the SCL-90-R aggression/hostility subscale and then correlated with cortical volume (VBM), and cortical thickness and gyrification. VBM analysis showed significant (P\u2009<\u20090.05, FDR-corrected at peak-level) positive correlations of cortical volume with SCL-90-R aggression subscale values in large clusters spanning bilateral anterior cingulate and orbitofrontal cortices and left lingual and postcentral gyri. Surface-based morphometry yielded mostly uncorrected positive correlations with cortical thickness in bilateral precentral gyri and with gyrification in left insula and superior temporal gyrus. Our findings imply an association of subclinical aggressive symptoms with cortical volume in areas important for emotion awareness and regulation, which might also be related to cortical adaptation to mental stress. These results overlap with several findings on impulsive aggression in patients suffering from affective and disruptive behavior disorders. They also suggest a biological symptom continuum manifesting in these brain areas. Hum Brain Mapp, 2017. \ua9 2017 Wiley Periodicals, Inc

From inflammation to degeneration – Enlarged perivascular spaces and glymphatic clearance in neuropsychiatric long-COVID syndrome

Neuropsychiatric symptoms, such as executive dysfunction, fatigue and depression, are highly prevalent and severely incapacitating among Long- and Post-COVID patients (Schou et al., 2021), to the point where some are unable to resume their jobs and even their daily lives. While the prognosis of these patients remains elusive, cognition worsens over time in many of them (Lu et al., 2020). Perivascular inflammation in the brain, as a consequence of the blood-brain barrier damage caused by SARS-CoV-2 (Yang et al., 2020), is one of the mechanisms of ongoing systemic and intracerebral inflammation proposed to contribute to these long-lasting symptoms. We thus investigated two surrogate measurements of glymphatics, enlarged perivascular spaces in T1-w magnetic resonance imaging and three-dimensional propagation of cardiorespiratory pulsations in ultrafast magnetic resonance encephalography (Barghoorn et al., 2021), in 60 neuropsychiatric long-COVID patients, 30 healthy COVID-19 survivors and 30 never-infected healthy controls. We provide evidence of EPVS burden being associated with cognitive impairment and cardiorespiratory pulsations slightly varying among these groups. We hypothesize glymphatic clearance dysfunction might be a way for post-COVID to transition into a neurodegenerative disorder