CAMK2-Dependent Signaling in Neurons Is Essential for Survival

Ca2+/calmodulin-dependent protein kinase II (CAMK2) is a key player in synaptic plasticity and memory formation. Mutations in Camk2a or Camk2b cause intellectual disability in humans, and severe plasticity and learning deficits in mice, indicating unique functions for each isoform. However, considering the high homology between CAMK2A and CAMK2B, it is conceivable that for critical functions, one isoform compensates for the absence of the other, and that the full functional spectrum of neuronal CAMK2 remains to be revealed.Here we show that germline as well as adult deletion of both CAMK2 isoforms in male or female mice is lethal. Moreover, Ca2+-dependent activity as well as autonomous activity of CAMK2 is essential for survival. Loss of both CAMK2 isoforms abolished LTP, whereas synaptic transmission remained intact. The double-mutants showed no gross morphological changes of the brain, and in contrast to the long-considered role for CAMK2 in the structural organization of the postsynaptic density (PSD), deletion of both CAMK2 isoforms did not affect the biochemical composition of the PSD. Together, these results reveal an essential role for CAMK2 signaling in early postnatal development as well as the mature brain, and indicate that the full spectrum of CAMK2 requirements cannot be revealed in the single mutants because of partial overlappin

Parameters gerelateerd aan een positieve testuitslag van FDG-PET(/CT) voor vasculitiden van de grote vaten

Objective: The purpose of this study is to identify clinical and analytical variables that may improve the effectiveness of the use of FDG-PET(/CT) scans for diagnosing large vessel vasculitis. Methods: A multicenter retrospective study of FDG-PET(/CT)scans performed between January 2000 and December 2009 for the diagnosis of large vessel vasculitis. Demographic data, clinical manifestations and analytical data prior to the scan were recorded. Results: A total of 304 FDG-PET(/CT) scans have been included, of which 62 are positive and 242 are negative for large vessel vasculitis. In the univariate analysis both groups differ significantly for age (65,9 ± 13,4 years versus 58,6 ± 16,5 years), female sex (76% versus 55%), a history of temporal arteritis (10% versus 3%), artralgia (31% versus 67%), thrombocytes (434 ± 161 x109/l versus 373 ± 168 x109/l) and ESR (72,6 ± 31,0 mm/hour versus 51,4 ± 30,5 mm/hour). In the multivariate analysis only artralgia (OR 11,0; 95%-CI 2,73 - 44,3) and ESR (OR 1,02; 95%-CI 1,00 - 1,05) remain statistical significant predictors for a positive test result. In the group with a positive test result none of the patients has a CRP of <10 mg/l, compared to 42 patients (26,1%) in the group with a positive test result (p<0,001). In 64% percent of the cases with a negative test result for large vessel vasculitis another diagnosis could eventually be made. In about half of the cases this alternative diagnosis was based on the results of the FDG PET(/CT) scan. Conclusions: The presence of artralgia and an elevated ESR are statistically significant predictors for a positive test result. However, in clinical practise it won’t be possible to reliably predict the outcome of the FDG-PET(/CT) scan based on these two variables. In patients with a CRP <10 mg/l performing a FDG-PET(/CT) scan for large vessel vasculitis seems to be useless.

Tissue culture and neurotoxicology

Application of tissue culture in neurotoxicology may serve two purposes. First, they may be used to unravel the mechanism of action of neurotoxic compounds and secondly, they may be used for the screening of neurotoxic agents. Studies belonging to the first group can be subdivided into those aiming at the replication of neurotoxic processes in vivo and into those concerned with non-specific effects of neurotoxicants on cultured cells. The potential usefulness of these types of studies for the development of screening methods is discussed. An investigation of acrylamide neurotoxicity in cultures of cerebral cells serves to illustrate such an approach. Chemicals/CAS: acrylamide, 79-06-1; colchicine, 64-86-8; glutathione, 70-18-8; nicotinamide adenine dinucleotide, 53-84-9; Acrylamide, 79-06-1; Acrylamides; Colchicine, 64-86-8; Glutathione, 70-18-8; NAD, 53-84-

N-alkane neurotoxicity in cultured cerebral cells

Chemicals/CAS: 2 hexanone, 591-78-6; acetonylacetone, 110-13-4; hexane, 110-54-

Measurement of the electrotonic length constant in cultured muscle fibres

The measurement of passive electrical membrane properties in cultured muscle cells is complicated by the fact that the electrotonic length in these cells often exceeds their actual length, leading to serious deviations from the simple infinite cable behaviour. By using very short current pulses for these measurements and integrating the responses, the cells can be made to behave as infinite cables

Trophic support by neural explants of cultured muscle fibers

The influence of various neural explants on the morphology and the survival of chick muscle fibers was studied. A method was developed to evaluate the condition of the muscle fibers using the following four morphological parameters: cross striation, thickness, number of fibers and absence of vacuoles. Chick as well as mouse spinal cord explants appeared to have a distinct favorable influence on the muscle fibers. Chick ciliary ganglia and mouse cortex explants had less effect and chick sympathetic ganglia and mouse dorsal root ganglia had no effect. Innervation by spinal cord neurons did not lead to a change in resting membrane potential of the muscle fibers. The amount of cross striation in muscle fibers in the vicinity of mouse spinal cord explants was positively correlated with the frequency of spontaneous end-plate potentials in the muscle fibers. d-Tubocurarine did not interfere with the trophic support of muscle cells by nerve cells, although it reversibly blocked neuromuscular transmission throughout the experiment. This demonstrates that neither the acetylcholine receptor nor the activity induced in the muscle fiber mediate the trophic action. The data suggest that a humoral trophic factor, released at the neuromuscular junction or at a region of close cell-cell contact, is needed for normal development and maintenance of muscle fiber morphology. Chemicals/CAS: acetylcholine, 51-84-3, 60-31-1, 66-23-9; tubocurarine chloride, 57-94-3, 57-95-4, 8006-51-

Effects of extracts of denervated muscles on the morphology of cultured muscle cells

Previously tropic effects of extracts from whole chick embryos and from innervated muscles on cultured muscle cells were described. The present study demonstrated similar effects of extracts from 10-days denervated chick muscles. Extracts from innervated as well as from denervated muscles exsanguinated in vivo with saline prior to dissection showed only marginal trophic activity, suggesting a major contribution of serum components to the trophic effects of tissue extracts. Indeed, serum of adult chicks appeared to have a trophic action similar to that of chick embryo extract

Lead exposure during demolition of a steel structure coated with lead-based paints. II. Reversible changes in the conduction velocity of the motor nerves in transiently exposed workers.

In a group of workers exposed to high levels of lead during five months nerve conduction velocity parameters were evaluated at the termination of exposure, and also three and fifteen months later. At the termination of exposure the mean blood lead level was 4.0 ??mol/l, and motor conduction velocities in the median and the ulnar nerves were slower and the distal latencies in the median nerve were longer compared to the values measured 15 months later. Sensory conduction velocities, measured distally in the same nerves, were not depressed compared to the values measured three or fifteen months later. It was tentatively concluded that the effect of lead on the conduction velocity of the motor nerves has an initial reversible phase, dependent on the duration of exposure. Chemicals/CAS: lead, 7439-92-1; Air Pollutants, Occupational; Lead, 7439-92-1 This work is licensed under a Creative Commons Attribution 4.0 International License