The effect of D-serine administration on cognition and mood in older adults

Abstract

// Marcos Avellar 1,2,* , Linda Scoriels 1,2,3,* , Caroline Madeira 1 , Charles Vargas-Lopes 1 , Priscila Marques 1 , Camila Dantas 1 , Alex C. Manhães 4 , Homero Leite 5 and Rogerio Panizzutti 1,2 1 Biomedical Sciences Institute, Federal University of Rio de Janeiro, RJ, Brazil 2 Institute of Psychiatry, Federal University of Rio de Janeiro, RJ, Brazil 3 Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom 4 Institute of Biology Roberto Alcantara Gomes, Biomedical Center, State University of Rio de Janeiro, RJ, Brazil 5 Integrated Unit for Prevention, Adventist Silvestre Hospital, Rio de Janeiro, RJ, Brazil * These authors contributed equally to this manuscript and should be referred to as joint first authors Correspondence to: Rogerio Panizzutti, email: // Keywords : D-serine, cognition, aging, glutamate metabolism, mood, Gerotarget Received : November 05, 2015 Accepted : January 30, 2016 Published : February 24, 2016 Abstract Background: D-serine is an endogenous co-agonist of the N-Methyl D-Aspartate Receptor (NMDAR) that plays a crucial role in cognition including learning processes and memory. Decreased D-serine levels have been associated with age-related decline in mechanisms of learning and memory in animal studies. Here, we asked whether D-serine administration in older adults improves cognition. Results: D-serine administration improved performance in the Groton Maze learning test of spatial memory and learning and problem solving (F (3, 38) = 4.74, p = 0.03). Subjects that achieved higher increases in plasma D-serine levels after administration improved more in test performance (r 2 =-0.19 p = 0.009). D-serine administration was not associated with any significant changes in the other cognitive tests or in the mood of older adults ( p > 0.05). Methods: Fifty healthy older adults received D-serine and placebo in a randomized, double blind, placebo-controlled, crossover design study. We studied the effect of D-serine administration on the performance of cognitive tests and an analogue mood scale. We also collected blood samples to measure D-serine, L-serine, glutamate and glutamine levels. Conclusions: D-serine administration may be a strategy to improve spatial memory, learning and problem solving in healthy older adults. Future studies should evaluate the impact of long-term D-serine administration on cognition in older adults.