1. Contribution of the D-Serine-dependent pathway to the cellular mechanisms underlying cognitive aging
- Author
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Emilie Rouaud, Catherine Videau, Fabrice R. Turpin, Pierre-Marie Sinet, Jean-Pierre Mothet, Jean-Marie Billard, Jacques Epelbaum, Patrick Dutar, Brigitte Potier, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de neurobiologie cellulaire et moléculaire (NBCM), and Centre National de la Recherche Scientifique (CNRS)
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Aging ,hippocampus ,Cognitive Neuroscience ,Hippocampus ,Review Article ,NMDA receptors ,lcsh:RC321-571 ,memory ,03 medical and health sciences ,0302 clinical medicine ,Metaplasticity ,serine racemase ,Aging brain ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,synaptic plasticity ,Long-term potentiation ,NMDA receptor ,Serine racemase ,Synaptic plasticity ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Depotentiation ,Psychology ,Neuroscience ,030217 neurology & neurosurgery - Abstract
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.
- Published
- 2010
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