Aging-Associated Cognitive Decline is Reversed by D-Serine Supplementation

Author:

Nava-Gómez L.,Calero-Vargas I.,Higinio-Rodríguez F.,Vázquez-Prieto B.,Olivares-Moreno R.,Ortiz-Retana J.,Aranda P.,Hernández-Chan N.,Rojas-Piloni G.,Alcauter S.,López-Hidalgo M.ORCID

Abstract

AbstractBrain aging is a natural process that involves structural and functional changes that lead to cognitive decline, even in healthy subjects. This detriment has been associated with NMDA receptor (NMDAR) hypofunction because of a reduction in the brain levels of D-serine, the endogenous NMDAR co-agonist. However, it is not clear whether D-serine supplementation could be used as an intervention to reduce or reverse age-related brain alterations. In the present work, we aimed to analyze the D-serine effect on aging-associated alterations in cellular and large-scale brain systems that could support cognitive flexibility in rats. We found that D-serine supplementation reverts the age-related decline in cognitive flexibility, frontal dendritic spine density, and partially restored large-scale functional connectivity without inducing nephrotoxicity; instead, D-serine restored the thickness of the renal epithelial cells that were affected by age. Our results suggest that D-serine could be used as a therapeutic target to reverse age-related brain alterations.

Funder

Consejo Nacional de Ciencia y Tecnología

UNAM | Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México

Publisher

Society for Neuroscience

Subject

General Medicine,General Neuroscience

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