Deregulation of NMDA-receptor function and down-stream signaling in APP[V717I] transgenic mice.

Evidence is accumulating for a role for amyloid peptides in impaired synaptic plasticity and cognition, while the underlying mechanisms remain unclear. We here analyzed the effects of amyloid peptides on NMDA-receptor function in vitro and in vivo. A synthetic amyloid peptide preparation containing monomeric and oligomeric A beta (1-42) peptides was used and demonstrated to bind to synapses expressing NMDA-receptors in cultured hippocampal and cortical neurons. Pre-incubation of primary neuronal cultures with A beta peptides significantly inhibited NMDA-receptor function, albeit not by a direct pharmacological inhibition of NMDA-receptors, since acute application of A beta peptides did not change NMDA-receptor currents in autaptic hippocampal cultures nor in xenopus oocytes expressing recombinant NMDA-receptors. Pre-incubation of primary neuronal cultures with A beta peptides however decreased NR2B-immunoreactive synaptic spines and surface expression of NR2B containing NMDA-receptors. Furthermore, we extended these findings for the first time in vivo, demonstrating decreased concentrations of NMDA-receptor subunit NR2B and PSD-95 as well as activated alpha-CaMKII in postsynaptic density preparations of APP[V717I] transgenic mice. This was associated with impaired NMDA-dependent LTP and decreased NMDA- and AMPA-receptor currents in hippocampal CA1 region in APP[V717I] transgenic mice. In addition, induction of c-Fos following cued and contextual fear conditioning was significantly impaired in the basolateral amygdala and hippocampus of APP[V717I] transgenic mice. Our data demonstrate defects in NMDA-receptor function and learning dependent signaling cascades in vivo in APP[V717I] transgenic mice and point to decreased surface expression of NMDA-receptors as a mechanism involved in early synaptic defects in APP[V717I] transgenic mice in vivo.

Determination of 75Se, 95Zr, 237Np and 241Am activities in Boom Clay samples from laboratory migration experiments using gamma-ray spectrometry

Percolation tests (i.e. routine laboratory migration experiments) have been performed to evaluate the diffusion behaviour of a number of long-lived radionuclides in Boom Clay, a candidate geological host formation for high level radioactive waste (HLW) in Belgium. Among the many potentially hazardous radionuclides under investigation are 79Se, 93Zr, 237Np, 241Am and 243Am. Actinide migration experiments have been carried out with 237Np and 241Am, while for the studies with Se and Zr the radioisotopes 75Se and 95Zr were used. Their transport patterns in the Boom Clay were examined using a combination of a NaI(Tl) detector and High-Purity Ge detectors either on the dissolved matrix (237Np, 241Am) or directly on the clay (75Se, 95Zr).

New fast preparation of 123I labelled radiopharmaceuticals.

A new fast kit preparation of 123I labelled radiopharmaceuticals such as IMP, HIPDM, MIBG and Hippuran is proposed. A radiochemical yield greater than 99% is obtained at 100 degrees C within 10-30 min. The new labelling procedure is based on the nucleophilic exchange in presence of Cu(I) and an excess of reducing agents. The four kit prepared 123I-radiopharmaceuticals have been used with success in clinical studies involving 400 patients. The proposed method is also compared with earlier described methods which, yielding labelled side products and 123I2, do not fulfill the requirements for kit labelling.