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Review ARTICLE

This article is part of a Research Topic

Contribution of the D-Serine-dependent pathway to the cellular mechanisms underlying cognitive aging

Brigitte Potier¹, Fabrice R . Turpin¹, Pierre-Marie Sinet¹, Emilie Rouaud¹, Jean-Pierre Mothet², Catherine Videau¹, Jacques Epelbaum¹, Patrick Dutar¹ and Jean-Marie Billard¹*

Centre de Psychiatrie et Neurosciences, INSERM, U894, Faculté de Médecine, Université Paris Descartes, Paris, France

Laboratoire de Neurobiologie Cellulaire et Moleculaire, CNRS UPR 9040, Gif sur Yvette, France

An association between age-related memory impairments and changes in functional plasticity in the aging brain has been under intense study within the last decade. In this article, we show that an impaired activation of the strychnine-insensitive glycine site of N-methyl-D-aspartate receptors (NMDA-R) by its agonist D-serine contributes to deficits of synaptic plasticity in the hippocampus of memory-impaired aged rats. Supplementation with exogenous D-serine prevents the age-related deficits of isolated NMDA-R-dependent synaptic potentials as well as those of theta-burst-induced long-term potentiation and synaptic depotentiation. Endogenous levels of d-serine are reduced in the hippocampus with aging, that correlates with a weaker expression of serine racemase synthesizing the amino acid. On the contrary, the affinity of D-serine binding to NMDA-R is not affected by aging. These results point to a critical role for the D-serine-dependent pathway in the functional alterations of the brain underlying memory impairment and provide key information in the search for new therapeutic strategies for the treatment of memory deficits in the elderly.

Keywords:

memory, serine racemase, NMDA receptors, hippocampus, synaptic plasticity

Citation:

Potier B, Turpin FR, Sinet P-M, Rouaud E, Mothet J-P, Videau C, Epelbaum J, Dutar P and Billard J-M (2010). Contribution of the D-Serine-dependent pathway to the cellular mechanisms underlying cognitive aging. Front. Ag. Neurosci. 2:1. doi:10.3389/neuro.24.001.2010

Received:

10 November 2009;

Paper pending published:

17 November 2009;

Accepted:

07 January 2010;

Published online:

05 February 2010.

Edited by:

Thomas C. Foster, University of Florida, USA

Reviewed by:

Jose M. Delgado-Garcia, University Pablo de Olavide, Spain
Michael R. Foy, Loyola Marymount University, USA
Michelle Nicolle, Wake Forest University, USA

© 2010 Potier, Turpin, Sinet, Rouaud, Mothet, Videau, Epelbaum, Dutar and Billard. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

*Correspondence:

Jean-Marie Billard, Centre de Psychiatrie et Neurosciences, INSERM, U894, Faculté de Médecine, Université Paris Descartes, 2 ter rue d’Alésia, 75014 Paris, France. e-mail: jean-marie.billard@inserm.fr