Riluzole restores memory and brain energy metabolism in AβPP-PS1 mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder leading to memory loss and impaired cognition. Despite several decades of research, AD therapeutic is not available. In this study, we have investigated the impact of a chronic intervention of riluzole on memory and neurometabolism in the AβPP-PS1 mouse model of AD. The 10-month-old AβPP-PS1 mice were administered 30 doses of riluzole (6 mg/kg, intragastrically) on an alternate day for two months. The memory was assessed using Morris Water Maze, while neurometabolism was evaluated by ¹H-[¹³C]-NMR spectroscopy together with an intravenous infusion of [1,6-¹³C₂]glucose. The normal saline-treated AβPP-PS1 mice exhibited a decrease in learning and memory that were restored to the control level following riluzole treatment. Most interestingly, the reduced ¹³C labeling of Glu_C4 and Asp_C3 from [1,6-¹³C]glucose in the AβPP-PS1 mice was restored to the control level following riluzole intervention. As a consequence, chronic riluzole treatment improved metabolic activity of glutamatergic neurons in AβPP-PS1 mice. Together these data suggest that riluzole may be useful for improving cognition in AD.