NCAM 180 Acting via a Conserved C-Terminal Domain and MLCK Is Essential for Effective Transmission with Repetitive Stimulation

SummaryNCAM 180 isoform null neuromuscular junctions are unable to effectively mobilize and exocytose synaptic vesicles and thus exhibit periods of total transmission failure during high-frequency repetitive stimulation. We have identified a highly conserved C-terminal (KENESKA) domain on NCAM that is required to maintain effective transmission and demonstrate that it acts via a pathway involving MLCK and probably myosin light chain (MLC) and myosin II. By perfecting a method of introducing peptides into adult NMJs, we tested the hypothesized role of proteins in this pathway by competitive disruption of protein-protein interactions. The effects of KENESKA and other peptides on MLCK and MLC activation and on failures in both wild-type and NCAM 180 null junctions supported this pathway, and serine phosphorylation of KENESKA was critical. We propose that this pathway is required to replenish synaptic vesicles utilized during high levels of exocytosis by facilitating myosin-driven delivery of synaptic vesicles to active zones or their subsequent exocytosis

Hip sonography update. Quality-management, catastrophes -tips and tricks

Abstract Aim: Hip sonography is today considered to be the diagnostic standard tool for developmental dysplasia of the hip (DDH) diagnosis. In Germany special commissions control the quality of the sonograms according to checklists to keep the standard high and to avoid over-and under -treatment. This paper lists tips and tricks to avoid typical mistakes according to these results. Material and method: In 8 German countries the quality of sonograms used to diagnose DDH was checked according to special checklists. An additional 250 medical doctors (pediatricians, radiologists, orthopaedic surgeons) were asked to classify 4 sonograms by measuring and typing. From the same group the projection (standing left, standing right, horizontal-cranial left, horizontal-cranial right) was checked according to the correct diagnosis in the shortest time. Results: In 1.6 % -43.7% the licence for hip sonography was withdrawn by the German commission. The best projection with the lowest rate of wrong interpretation was the "standing right"-projection. Most of the mistakes were made because of a wrong anatomical identification and usability check. Conclusion: Hip sonography must be trained by authorized teachers. The quality of the sonograms must be controlled according to checklists. The bedside teaching without control leads to a systematic teaching of mistakes and finally catastrophes

Exposure to mild blast forces induces neuropathological effects, neurophysiological deficits and biochemical changes

Direct or indirect exposure to an explosion can induce traumatic brain injury (TBI) of various severity levels. Primary TBI from blast exposure is commonly characterized by internal injuries, such as vascular damage, neuronal injury, and contusion, without external injuries. Current animal models of blast-induced TBI (bTBI) have helped to understand the deleterious effects of moderate to severe blast forces. However, the neurological effects of mild blast forces remain poorly characterized. Here, we investigated the effects caused by mild blast forces combining neuropathological, histological, biochemical and neurophysiological analysis. For this purpose, we employed a rodent blast TBI model with blast forces below the level that causes macroscopic neuropathological changes. We found that mild blast forces induced neuroinflammation in cerebral cortex, striatum and hippocampus. Moreover, mild blast triggered microvascular damage and axonal injury. Furthermore, mild blast caused deficits in hippocampal short-term plasticity and synaptic excitability, but no impairments in long-term potentiation. Finally, mild blast exposure induced proteolytic cleavage of spectrin and the cyclin-dependent kinase 5 activator, p35 in hippocampus. Together, these findings show that mild blast forces can cause aberrant neurological changes that critically impact neuronal functions. These results are consistent with the idea that mild blast forces may induce subclinical pathophysiological changes that may contribute to neurological and psychiatric disorders

Brain Deletion of Insulin Receptor Substrate 2 Disrupts Hippocampal Synaptic Plasticity and Metaplasticity

Diabetes mellitus is associated with cognitive deficits and an increased risk of dementia, particularly in the elderly. These deficits and the corresponding neurophysiological structural and functional alterations are linked to both metabolic and vascular changes, related to chronic hyperglycaemia, but probably also defects in insulin action in the brain. To elucidate the specific role of brain insulin signalling in neuronal functions that are relevant for cognitive processes we have investigated the behaviour of neurons and synaptic plasticity in the hippocampus of mice lacking the insulin receptor substrate protein 2 (IRS-2)

alphaCaMKII autophosphorylation:a fast track to memory

Alpha Ca2+/calmodulin-dependent kinase II (alpha-CaMKII), the major synaptic protein in the forebrain, can switch into a state of autonomous activity upon autophosphorylation. It has been proposed that alpha CaMKII autophosphorylation mediates long-term memory (LTM) storage. However, recent evidence shows that synaptic stimulation and behavioural training only transiently increase the autonomous alpha CaMKII activity, implicating alpha CaMKII autophosphorylation in LTM formation rather than storage. Consistent with this, mutant mice deficient in alpha CaMKII autophosphorylation can store LTM after a massed training protocol, but cannot form LTM after a single trial. Here, we review evidence that the role of alpha CaMKII autophosphorylation is in fact to enable LTM formation after a single training trial, possibly by regulating LTM consolidation-specific transcription