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Contribution of the d-Serine-Dependent Pathway to the Cellular Mechanisms Underlying Cognitive Aging.

Potier B, Turpin FR, Sinet PM, Rouaud E, Mothet JP, Videau C, Epelbaum J, Dutar P, Billard JM - Front Aging Neurosci (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus

d-serine alleviates the age-related deficit in synaptic plasticity. (A, left) Effects of d-serine (100 μM) on the magnitude of HFS-induced LTP calculated for the last 15 min of recording. (A, right) Time-course of LTP induced in adult and aged rats in the presence of the NMDA-R co-agonist. (B, C) Results obtained with TBS and depotentiation protocols respectively (#p < 0.05, ##p < 0.01, unpaired t-test).
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Figure 3: d-serine alleviates the age-related deficit in synaptic plasticity. (A, left) Effects of d-serine (100 μM) on the magnitude of HFS-induced LTP calculated for the last 15 min of recording. (A, right) Time-course of LTP induced in adult and aged rats in the presence of the NMDA-R co-agonist. (B, C) Results obtained with TBS and depotentiation protocols respectively (#p < 0.05, ##p < 0.01, unpaired t-test).

Mentions: In slices from adults (n = 12), d-serine did not affect the magnitude of HFS-induced LTP, whereas it significantly increased the amplitude of potentiation in slices (n = 10) from old animals (p < 0.05, Figure 3A, left). Under these conditions, in which the agonist saturated the glycine binding sites of the NMDA-R, HFS-induced LTP was higher in aged rats (77.8 ± 13.9%) than in younger ones (55 ± 11.6%) (Figure 3A, right), although this difference was not statistically relevant.


Contribution of the d-Serine-Dependent Pathway to the Cellular Mechanisms Underlying Cognitive Aging.

Potier B, Turpin FR, Sinet PM, Rouaud E, Mothet JP, Videau C, Epelbaum J, Dutar P, Billard JM - Front Aging Neurosci (2010)

d-serine alleviates the age-related deficit in synaptic plasticity. (A, left) Effects of d-serine (100 μM) on the magnitude of HFS-induced LTP calculated for the last 15 min of recording. (A, right) Time-course of LTP induced in adult and aged rats in the presence of the NMDA-R co-agonist. (B, C) Results obtained with TBS and depotentiation protocols respectively (#p < 0.05, ##p < 0.01, unpaired t-test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874399&req=5

Figure 3: d-serine alleviates the age-related deficit in synaptic plasticity. (A, left) Effects of d-serine (100 μM) on the magnitude of HFS-induced LTP calculated for the last 15 min of recording. (A, right) Time-course of LTP induced in adult and aged rats in the presence of the NMDA-R co-agonist. (B, C) Results obtained with TBS and depotentiation protocols respectively (#p < 0.05, ##p < 0.01, unpaired t-test).
Mentions: In slices from adults (n = 12), d-serine did not affect the magnitude of HFS-induced LTP, whereas it significantly increased the amplitude of potentiation in slices (n = 10) from old animals (p < 0.05, Figure 3A, left). Under these conditions, in which the agonist saturated the glycine binding sites of the NMDA-R, HFS-induced LTP was higher in aged rats (77.8 ± 13.9%) than in younger ones (55 ± 11.6%) (Figure 3A, right), although this difference was not statistically relevant.

Bottom Line: 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.

View Article: PubMed Central - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus