Research Papers: Gerotarget (Focus on Aging):

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

Marcos Avellar _, Linda Scoriels, Caroline Madeira, Charles Vargas-Lopes, Priscila Marques, Camila Dantas, Alex C. Manhães, Homero Leite and Rogerio Panizzutti

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Oncotarget. 2016; 7:11881-11888. https://doi.org/10.18632/oncotarget.7691

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Marcos Avellar1,2,*, Linda Scoriels1,2,3,*, Caroline Madeira1, Charles Vargas-Lopes1, Priscila Marques1, Camila Dantas1, Alex C. Manhães4, Homero Leite5 and Rogerio Panizzutti1,2

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


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 (r2=-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.

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