Dissociation of genotype-dependent cognitive and motor behavior in a strain of aging mice devoid of the prion protein.

The prion glycoprotein (PrPC) is highly expressed in the nervous system as well as in other organs. Its functional roles in behavior have been examined mainly in non co-isogenic, wild-type and PrPC-deficient mice, which showed both age- and genotype-dependent differences. In general, however, effects of genetic background upon behavioral tests are mostly unclear when applied to aging rodents. The present study aimed to determine the effect of deletion of the prion protein on behavior of isogenic mice across different ages. We disclosed a genotype-dependent behavioral dissociation between either motor or cognitive tests, as a function of both age and test type. Remarkably, we also detected a clear age- and genotype-dependent difference in the variability of performance in a cognitive test. The current findings are relevant for both the interpretation of PrPC-related behavior, as well as for issues of reproducibility in studies of rodent behavior.

LipoCardium: endothelium-directed cyclopentenone prostaglandin-based liposome formulation that completely reverses atherosclerotic lesions.

Atherosclerosis is a multifactorial inflammatory disease of blood vessels which decimates one in every three people in industrialized world. Despite the important newest clinical approaches, currently available strategies (e.g. nutritional, pharmacological and surgical) may only restrain the worsening of vascular disease. Since antiproliferative cyclopentenone prostaglandins (CP-PGs) are powerful anti-inflammatory agents, we developed a negatively charged liposome-based pharmaceutical formulation (LipoCardium) that specifically direct CP-PGs towards the injured arterial wall cells of atherosclerotic mice. In the blood stream, LipoCardium delivers its CP-PG contents only into activated arterial wall lining cells due to the presence of antibodies raised against vascular cell adhesion molecule-1 (VCAM-1), which is strongly expressed upon inflammation by endothelial cells and macrophage-foam cells as well. After 4 months in a high-lipid diet, all low-density lipoprotein receptor-deficient adult control mice died from myocardium infarction or stroke in less than 2 weeks, whereas LipoCardium-treated (2 weeks) animals (still under high-lipid diet) completely recovered from vascular injuries. In vitro studies using macrophage-foam cells suggested a tetravalent pattern for LipoCardium action: anti-inflammatory, antiproliferative (and pro-apoptotic only to foam cells), antilipogenic and cytoprotector (via heat-shock protein induction). These astonishing cellular effects were accompanied by a marked reduction in arterial wall thickness, neointimal hyperplasia and lipid accumulation, while guaranteed lifespan to be extended to the elderly age. Our findings suggest that LipoCardium may be safely tested in humans in a near future and may have conceptual implications in atherosclerosis therapy.