D-Serine in the aging hippocampus

Journal of Pharmaceutical and Biomedical Analysis
Jean-Marie Billard

Abstract

Experimental evidences now indicate that memory formation relies on the capacity of neuronal networks to manage long-term changes in synaptic communication. This property is driven by N-methyl-D-aspartate receptors (NMDAR), which requires the binding of glutamate but also the presence of the co-agonist D-serine at the glycine site. Defective memory function and impaired brain synaptic plasticity observed in aging are rescued by partial agonist acting at this site suggesting that this gating process is targeted to induce age-related cognitive defects. This review aims at compelling recent studies characterizing the role of D-serine in changes in functional plasticity that occur in the aging hippocampus since deficits are rescued by D-serine supplementation. The impaired efficacy of endogenous D-serine is not due to changes in the affinity to glycine-binding site but to a decrease in tissue levels of the amino acid resulting from a weaker expression of the producing enzyme serine racemase (SR). Interestingly, neither SR expression, D-serine levels, nor NMDAR activation is affected in aged LOU/C rats, a model of healthy aging in which memory deficits do not occur. These old animals do not develop oxidative stress suggesting that t...Continue Reading

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Feb 21, 2018·Frontiers in Psychiatry·Gerson D Guercio, Rogerio Panizzutti
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