Evaluation of new generation translocator protein ligand efficacy in a mouse model of Alzheimer`s disease.

Outline of Final Research Achievements

Our previous work has demonstrated that ligands of the translocator protein (TSPO) are protective in a mouse model of Alzheimer`s disease. The purpose of this study was to characterize the potential suitability of three new generation TSPO ligands. We tested the ability of the new generation TSPO ligands to penetrate the brain of living mice, as well as their ability to bind TSPO in human brain sections. Next we assessed their effect on memory, anxiety and depression-related behaviors in mice. All three TSPO ligands improved memory function and one also reduced depression-related behavior. TSPO ligands are thought to improve memory by increasing brain hormone production. Confirming this mechanism of action, memory improvements in TSPO-ligand treated mice were blocked by inhibition of hormone production. Our findings indicate these new TSPO ligands may be promising therapeutic candidates for the treatment of Alzheimer`s disease.