Neuronal deletion of the circadian clock gene Bmal1 induces cell-autonomous dopaminergic neurodegeneration

Circadian rhythm dysfunction is a hallmark of Parkinson disease (PD), and diminished expression of the core clock gene Bmal1 has been described in patients with PD. BMAL1 is required for core circadian clock function but also serves nonrhythmic functions. Germline Bmal1 deletion can cause brain oxidative stress and synapse loss in mice, and it can exacerbate dopaminergic neurodegeneration in response to the toxin MPTP. Here we examined the effect of cell type-specific Bmal1 deletion on dopaminergic neuron viability in vivo. We observed that global, postnatal deletion of Bmal1 caused spontaneous loss of tyrosine hydroxylase+ (TH+) dopaminergic neurons in the substantia nigra pars compacta (SNpc). This was not replicated by light-induced disruption of behavioral circadian rhythms and was not induced by astrocyte- or microglia-specific Bmal1 deletion. However, either pan-neuronal or TH neuron-specific Bmal1 deletion caused cell-autonomous loss of TH+ neurons in the SNpc. Bmal1 deletion did not change the percentage of TH neuron loss after α-synuclein fibril injection, though Bmal1-KO mice had fewer TH neurons at baseline. Transcriptomics analysis revealed dysregulation of pathways involved in oxidative phosphorylation and Parkinson disease. These findings demonstrate a cell-autonomous role for BMAL1 in regulating dopaminergic neuronal survival and may have important implications for neuroprotection in PD

Entscheidungsfindung im Schwangerschaftskonflikt : einflussnehmende Faktoren und systemische Unterstützungsmöglichkeiten

Die Bachelorarbeit handelt davon wie der systemische Beratungsansatz Klientinnen in der Schwangerschaftskonfliktberatung unterstützen kann, zu einer bewussten Entscheidung zu gelangen. Hierzu werden im Vorfeld wesentliche Aspekte, die Bestandteile eines Schwangerschaftskonfliktes sein können, beleuchtet. Danach werden die äußeren Rahmenbedingungen der Konfliktberatung, die auf diese einwirken betrachtet. Es schließen sich die Grundlagen der systemischen Beratung an. Mit der Thematisierung verschiedener Lebenswelten, mit denen Klientinnen an die Beratung herantreten, bahnt sich der Fokus den Weg zur Beratungssituation. Der Hauptteil wird eingeleitet durch die Überlegung, auf welcher Basis die Entscheidungsfindung eines Schwangerschaftskonfliktes fußt, woran sich ergänzende Beratungsaspekte von Menschen in schwierigen Lebenssituationen anschließen. Im Folgenden werden systemische Methoden vorgestellt, welche zusammen mit dem erarbeiteten Gegenstand der Schwangerschaftskonfliktberatung als Grundlage für die Umsetzung dienen. In dieser erfahren einige Inhalte der Konfliktberatung systemische Erarbeitung und machen deutlich wie die Auseinandersetzung aus neuen Perspektiven gefördert und Handlungsoptionen erweitert werden können. Abgerundet wird der Hauptteil mit der Frage wie der Partner, mithilfe systemischen Ansatzes, in einer Konfliktberatung konstruktiv berücksichtigt werden kann, bevor ein abschließender Blick auf die Arbeit folgt

Cognitive Mediators of Intoxication: Self-Efficacy and Attribution in Marlatt's Abstinence Violation Effect.

This study was designed to assess Marlatt's proposed abstinence violation effect, which states that alcohol users who fail to ingest in line with their subjective limits on consumption will attribute that failure to internal causes, decline in self-efficacy, and give up further regulation of consumption. Marlatt also proposed that drinkers high in self-efficacy may react differently to initial counternormative ingestion than drinkers low in self-efficacy. Forty-eight, male, non-alcoholic, heavy social drinkers recruited from the general population were asked to volunteer to consume their usual initial amount of fluid from a preliminary placebo beverage presented as vodka and tonic. Half the subjects were informed that they had consumed more than their limit. The subjects reported their attributions and self-efficacy, and performed a taste-rating task using placebo beverages. Differences in taste test consumption, in change of self-efficacy between preexperimental and experimental assessments, and in attributions for the initial ingestion were then assessed by two-way analyses of variance using a 2 x 2 (experimental/control versus high/low preexperimental self efficacy) between subjects design. Subjects were then restratified on the basis of taste test consumption. Change in self-efficacy and attribution for initial ingestion were then analyzed via two-way analyses of variance using a 2 x 2 (experimental/control versus low/high consumers) between subjects design. The results of the present study did not support Marlatt's entire abstinence violation effect but did indicate that both the drinker's sense of self-efficacy and his attributional processes can influence alcohol use. Instructed subjects did not differ from control subjects. Subjects low in preexperimental self-efficacy consumed more beverage than did high self-efficacy subjects. High consumers made different attributions than did low consumers.Ph.D.School counselingUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/160062/1/8412275.pd