Axonal projection‐specific differences in somatodendritic α2 autoreceptor function in locus coeruleus neurons

The locus coeruleus (LC) contains the majority of central noradrenergic neurons sending wide projections throughout the entire CNS. The LC is considered to be essential for multiple key brain functions including arousal, attention and adaptive stress responses as well as higher cognitive functions and memory. Electrophysiological studies of LC neurons have identified several characteristic functional features such as low‐frequency pacemaker activity with broad action potentials, transient high‐frequency burst discharges in response to salient stimuli and an apparently homogeneous inhibition of firing by activation of somatodendritic α2 autoreceptors (α2AR). While stress‐mediated plasticity of the α2AR response has been described, it is currently unclear whether different LC neurons projecting to distinct axonal targets display differences in α2AR function. Using fluorescent beads‐mediated retrograde tracing in adult C57Bl6/N mice, we compared the anatomical distributions and functional in vitro properties of identified LC neurons projecting either to medial prefrontal cortex, hippocampus or cerebellum. The functional in vitro analysis of LC neurons confirmed their mostly uniform functional properties regarding action potential generation and pacemaker firing. However, we identified significant differences in tonic and evoked α2AR‐mediated responses. While hippocampal‐projecting LC neurons were partially inhibited by endogenous levels of norepinephrine and almost completely silenced by application of saturating concentrations of the α2 agonist clonidine, prefrontal‐projecting LC neurons were not affected by endogenous levels of norepinephrine and only partially inhibited by saturating concentrations of clonidine. Thus, we identified a limited α2AR control of electrical activity for prefrontal‐projecting LC neurons indicative of functional heterogeneity in the LC‐noradrenergic system.     

Plötzlicher Herz-Kreislauf-Stillstand und Reanimation im Sport

Notfall + Rettungsmedizin - Der plötzliche Herz-Kreislauf-Stillstand im Sport ist ein seltenes, aber manchmal ein besonders eindrückliches Ereignis, wie man anhand der Krankengeschichte...     

Notärztliches Atemwegsmanagement in Abhängigkeit von Fachrichtung und Weiterbildung

Die Anaesthesiologie - Das Management des schwierigen Atemwegs ist eine präklinische Schlüsselqualifikation. Für Notärzte mit hohem Erfahrungsgrad im Atemwegsmanagement sind...     

Melatonin compensates silencing of heat shock protein 70 and suppresses ultraviolet radiation‐induced inflammation in human skin ex vivo and cultured keratinocytes

Melatonin, a lipophilic compound synthesized and released from the pineal gland, effectively acts against ultraviolet radiation (UVR), one of the main inducers of epidermal damage, skin cancer, inflammation, and DNA photo damage. One of the common known stress protein induced by UVR is heat shock protein 70 (Hsp70), highly expressed in human keratinocytes, providing cellular resistance to such stressors. Here, using human full‐thickness skin and normal human epidermal keratinocytes (NHEK), we investigated the interaction of melatonin and Hsp70 toward UVR‐induced inflammatory and apoptotic responses. The following observations were made: (i) UVR upregulated Hsp70 gene expression in human epidermis while melatonin significantly inverted this effect, (ii) similar patterns of regulation were observed within Hsp70 protein level, and (iii) mechanistic studies involving silencing of Hsp70 RNA (Hsp70 siRNA) showed prominent decrease of IκB‐α (an inhibitor of NF‐κB) and enhanced gene expression of pro‐inflammatory cytokines (IL‐1β, IL‐6, Casp‐1) and pro‐apoptotic protein (Casp‐3) in NHEK. Parallel investigation using melatonin (10^?3 m ) significantly inverted these responses regardless depletion of Hsp70 RNA suggesting a compensatory action of this compound in the defense mechanisms. Our findings combined with data reported so far thus enrich existing knowledge about the potent anti‐apoptotic and anti‐inflammatory action of melatonin.     

Health Care Utilization After Ventricular Tachycardia Ablation: A Propensity Score-Matched Cohort Study

Background

Catheter ablation of ventricular tachycardia (VT) can reduce the burden of ventricular arrhythmia (VA) but its effect on health care utilization and costs after such therapy is poorly known. We sought to compare the rates of cardiovascular (CV)-related hospitalizations, survival, and health care costs in patients with recurrent VT treated either with VT ablation or with medical therapy.