TY - JOUR T1 - Aging-Associated Cognitive Decline is Reversed by D-Serine Supplementation JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0176-22.2022 VL - 9 IS - 3 SP - ENEURO.0176-22.2022 AU - L. Nava-Gómez AU - I. Calero-Vargas AU - F. Higinio-Rodríguez AU - B. Vázquez-Prieto AU - R. Olivares-Moreno AU - J. Ortiz-Retana AU - P. Aranda AU - N. Hernández-Chan AU - G. Rojas-Piloni AU - S. Alcauter AU - M. López-Hidalgo Y1 - 2022/05/01 UR - http://www.eneuro.org/content/9/3/ENEURO.0176-22.2022.abstract N2 - Brain 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. ER -