PT  - JOURNAL ARTICLE
AU  - Nava-Gómez, L.
AU  - Calero-Vargas, I.
AU  - Higinio-Rodríguez, F.
AU  - Vázquez-Prieto, B.
AU  - Olivares-Moreno, R.
AU  - Ortiz-Retana, J.
AU  - Aranda, P.
AU  - Hernández-Chan, N.
AU  - Rojas-Piloni, G.
AU  - Alcauter, S.
AU  - López-Hidalgo, M.
TI  - AGING-ASSOCIATED COGNITIVE DECLINE IS REVERSED BY D-SERINE SUPPLEMENTATION
AID  - 10.1523/ENEURO.0176-22.2022
DP  - 2022 May 18
TA  - eneuro
PG  - ENEURO.0176-22.2022
4099  - http://www.eneuro.org/content/early/2022/05/17/ENEURO.0176-22.2022.short
4100  - http://www.eneuro.org/content/early/2022/05/17/ENEURO.0176-22.2022.full
AB  - 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 N-methyl-D-aspartate receptor (NMDAR) hypofunction due to a reduction in the brain levels of D-serine, the endogenous NMDAR co-agonist. However, it is not clear if 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.SIGNIFICANT STATEMENTAge-related behavioral changes in cognitive performance occur as a physiological process of aging. Then, it is important to explore possible therapeutics to decrease, retard or reverse aging effects on the brain. NMDA receptor hypofunction contributes to the aging-associated cognitive decline. In the aged brain, there is a reduction in the brain levels of the NMDAR co-agonist, D-Serine. However, it is unclear if chronic D-serine supplementation could revert the age-detriment in brain functions. Our results show that D-serine supplementation reverts the age-associated decrease in cognitive flexibility, functional brain connectivity, and neuronal morphology. Our findings raise the possibility that restoring the brain levels of D-serine could be used as a therapeutic target to recover brain alterations associated with aging.