The battle of Alzheimer's Disease - the beginning of the future Unleashing the potential of academic discoveries.

Alzheimer's Disease (AD) is the most common form of dementia, affecting approximately 36 million people worldwide. To date there is no preventive or curative treatment available for AD, and in absence of major progress in therapeutic development, AD manifests a concrete socioeconomic threat. The awareness of the growing problem of AD is increasing, exemplified by the recent G8 Dementia Summit, a meeting held in order to set the stage and steer the compass for the future.

Effects of GABA agonists on body temperature regulation in GABA(B(1))-/- mice.

1. Activation of GABA(B) receptors evokes hypothermia in wildtype (GABA(B(1))+/+) but not in GABA(B) receptor knockout (GABA(B(1))-/-) mice. The aim of the present study was to determine the hypothermic and behavioural effects of the putative GABA(B) receptor agonist gamma-hydroxybutyrate (GHB), and of the GABA(A) receptor agonist muscimol.

Deletion of neuropeptide Y (NPY) 2 receptor in mice results in blockage of NPY-induced angiogenesis and delayed wound healing.

Neuropeptide Y (NPY), a 36-aa peptide, is widely distributed in the brain and peripheral tissues. Whereas physiological roles of NPY as a hormoneneurotransmitter have been well studied, little is known about its other peripheral functions. Here, we report that NPY acts as a potent angiogenic factor in vivo using the mouse corneal micropocket and the chick chorioallantoic membrane (CAM) assays.

Effects of repeated administration of baclofen to rats on GABAB receptor binding sites and subunit expression in the brain.

Repeated stimulation of the GABAB receptor with baclofen frequently produces tolerance, the underlying mechanisms of which are poorly understood. The purpose of the present work was to determine whether repeated administration of baclofen to rats is accompanied by changes in cerebral GABAB receptor binding sites, mRNA for the subunits GABAB(1) and GABAB(2), and protein levels for these subunits. Rats were injected with placebo or baclofen (20 micromol/kg subcutaneously) once daily for 14 days.

Attenuation of hypercholesterolemia and hyperglycemia in ob/ob mice by NPY Y2 receptor ablation.

Neuropeptide Y (NPY) is a 36 amino acid peptide well known for its role in regulating food intake and energy homeostasis. It has previously been shown that the NPY Y2 receptor is required for a full biological response to leptin in the central nervous system. We have examined the impact of this receptor on plasma levels of lipid and cholesterol in wild type and obese (ob/ob) mice.

Neuropeptide Y Y1 and neuropeptide Y Y2 receptors in human cardiovascular tissues.

mRNA encoding the human NPY Y1 and NPY Y2 receptors were detected in cerebral, meningeal, and coronary arteries using reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, the trigeminal and superior cervical ganglia were positive for both receptors. In some arteries and in SK-N-MC cells only mRNA encoding the NPY Y1 was detected.

Intron-mediated expression of the human neuropeptide Y Y1 receptor.

The Neuropeptide Y (NPY) family of neuropeptides exert their function through a family of heptahelical G-protein coupled receptors regulating essential physiological processes. A 97 base pair intron (intron IV) intervenes the coding sequence of the human NPY Y1 receptor (hY1) gene and was found frequently retained at variable levels in poly A+ mRNA isolated from multiple human tissues. When included in hY1 expression vectors, either in its natural position or 5' of the hY1 cDNA, intron IV mediated a significant increase of both hY1 mRNA and corresponding functional receptor protein in transfected mammalian cells, implying an in vivo regulatory function of the endogenous intron.

Inability of 50 Hz magnetic fields to regulate PKC- and Ca(2+)-dependent gene expression in Jurkat cells.

We have previously reported that the T cell line Jurkat registers the exposure of a sinusoidal extremely low frequency magnetic field at the level of the plasma membrane, resulting in activation of the tyrosine kinase p56(lck), increase in inositol-3-phosphate levels and increase in intracellular calcium concentration within minutes. To elucidate if these events associated with changes in intracellular calcium ion levels were biologically significant, transient transfections of Jurkat cells were performed with calcium-ion dependent reporter constructs. Three different enhancer/promoter constructs were studied coupled to the luciferase reporter gene.