Improved NMDA Receptor Activation by the Secreted Amyloid-Protein Precursor-α in Healthy Aging: A Role for D-Serine? - Normandie Université Access content directly
Journal Articles International Journal of Molecular Sciences Year : 2022

Improved NMDA Receptor Activation by the Secreted Amyloid-Protein Precursor-α in Healthy Aging: A Role for D-Serine?

Thomas Freret

Abstract

Impaired activation of the N-methyl-D-aspartate subtype of glutamate receptors (NMDAR) by D-serine is linked to cognitive aging. Whether this deregulation may be used to initiate pharmacological strategies has yet to be considered. To this end, we performed electrophysiological extracellular recordings at CA3/CA1 synapses in hippocampal slices from young and aged mice. We show that 0.1 nM of the soluble N-terminal recombinant fragment of the secreted amyloidprotein precursor-α (sAPPα) added in the bath significantly increased NMDAR activation in aged but not adult mice without impacting basal synaptic transmission. In addition, sAPPα rescued the age-related deficit of theta-burst-induced long-term potentiation. Significant NMDAR improvement occurred in adult mice when sAPPα was raised to 1 nM, and this effect was drastically reduced in transgenic mice deprived of D-serine through genetic deletion of the synthesizing enzyme serine racemase. Altogether, these results emphasize the interest to consider sAPPα treatment targeting D-serine-dependent NMDAR deregulation to alleviate cognitive aging.
Fichier principal
Vignette du fichier
IJMS 2022.pdf (2.66 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-03910923 , version 1 (22-12-2022)

Identifiers

Cite

Jean-Marie Billard, Thomas Freret. Improved NMDA Receptor Activation by the Secreted Amyloid-Protein Precursor-α in Healthy Aging: A Role for D-Serine?. International Journal of Molecular Sciences, 2022, 23, ⟨10.3390/ijms232415542⟩. ⟨hal-03910923⟩
8 View
15 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More