Latest Publications
MSK1 is required for the experience- and ampakine-dependent enhancement of spatial reference memory and reversal learning and for the induction of Arc and BDNF
Lorenzo Morè, Lucia Privitera, Marcia Lopes, J. Simon C. Arthur, Julie C. Lauterborn, Sonia A.L. Corrêa, Bruno G. Frenguelli
One class of cognitive enhancers, the ampakines, has attracted particular attention by virtue of improving cognition associated with animal models of neurodevelopmental, neurodegenerative, and psychiatric conditions, as well as in age-related cognitive impairment. Ampakines elevate CNS levels of BDNF, and it is through this elevation that their beneficial actions are believed to occur. To establish whether MSK1 converts ampakine-induced elevations of BDNF into cognitive enhancement we tested an ampakine (CX929) in male WT mice and in male mice in which the kinase activity of MSK1 was inactivated. We found that MSK1 is required for the ampakine-dependent improvement in spatial reference memory and cognitive flexibility, and for the elevations of BDNF and the plasticity-related protein Arc associated with ampakines and experience. These observations implicate MSK1 as a key enabler of the beneficial effects of ampakines on cognitive function, and furthermore identify MSK1 as a hub for BDNF-elevating nootropic strategies.