023). Our results indicate that sex modulates the interactive effect of the 5-HTTLPR genotype and CA on hippocampal volume. While the S’-allele is associated with hippocampal volume independent

of CA in women, men only have smaller hippocarnpi if they carry the risk allele and experienced severe CA. Neuropsychopharmacology (2012) 37, 1848-1855; doi:10.1038/npp.2012.32; published online 21 March 2012″
“The cholinergic system is involved in cognition as well as in age-related cognitive decline and Alzheimer disease (AD). Cholinergic enhancers ameliorate AD symptoms and represent the main current therapy for AD. MTC (Methylthioninium chloride), an antioxidant with metabolism-enhancing properties may be a novel candidate

selleck kinase inhibitor with pro-cognitive capacities.

This study was performed: (1) to assess the Nirogacestat concentration pro-cognitive efficacy of MTC and establish its dose-response; (2) to compare the efficacy of MTC with rivastigmine and (3) to determine the potential for combination therapy by co-administration of MTC and rivastigmine.

Spatial cognition of female NMRI mice was tested in a reference memory water maze task. Subjects received intra-peritoneal injections of scopolamine (0.5 mg/kg) followed by vehicle, and/or MTC and/or rivastigmine (0.15-4 mg/kg MTC; 0.1-0.5 mg/kg rivastigmine) in mono or combination treatment.

Scopolamine treatment prevented spatial Suplatast tosilate learning in NMRI female mice and the deficit was reversed by both rivastigmine and MTC in a dose-dependent manner. Mono-therapy with high doses of rivastigmine (> 0.5 mg/kg) caused severe side effects but MTC was safe up to 4 mg/kg. Co-administration of sub-effective doses of both drugs acted synergistically in reversing learning deficits and scopolamine-induced memory impairments.

In our model, MTC reversed the spatial learning impairment. When combined with the ChEI rivastigmine, the effect of MTC appeared to be amplified indicating that combination therapy could potentially improve not only symptoms but also contribute beneficially to neuronal metabolism

by minimising side effects at lower doses.”
“Reactive oxygen species (ROS), particularly hydrogen peroxide, and the proteins that regulate them play important roles in the migration and adhesion of cells. Stimulation of cell surface receptors with growth factors and chemoattractants generates ROS, which relay signals from the cell surface to key signaling proteins inside the cell. ROS act within cells to promote migration and also in nonmigrating cells to influence the behavior of migrating cells. Hydrogen peroxide has also been suggested to act as a chemoattractant in its own right, drawing immune cells to wounds. We discuss recent progress made towards understanding how organisms use ROS, and to what degree they depend on them, during the related processes of cell migration and adhesion.