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

L Nava-Gómez1,2, I Calero-Vargas1,3, F Higinio-Rodríguez1,3

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D-serine supplementation reversed age-related cognitive decline and brain changes in rats. This suggests D-serine may be a therapeutic target for age-related brain alterations.

Keywords:
D-serineagingcognitive flexibilityfMRIfunctional brain connectivity

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Area of Science:

  • Neuroscience
  • Aging Research
  • Pharmacology

Background:

  • Brain aging naturally causes cognitive decline, linked to reduced N-methyl-D-aspartate receptor (NMDAR) function due to lower D-serine levels.
  • The potential of D-serine supplementation to counteract these age-related brain changes remains unclear.

Purpose of the Study:

  • To investigate the effects of D-serine supplementation on aging-associated alterations in cellular and large-scale brain systems in rats.
  • To assess D-serine's impact on cognitive flexibility and neuronal morphology in aging.

Main Methods:

  • Administered D-serine to aging rats.
  • Assessed cognitive flexibility using behavioral tests.
  • Analyzed frontal dendritic spine density and large-scale functional brain connectivity.
  • Evaluated for nephrotoxicity and effects on kidney structure.

Main Results:

  • D-serine supplementation reversed age-related decline in cognitive flexibility.
  • Restored frontal dendritic spine density and partially improved large-scale functional connectivity.
  • Did not induce nephrotoxicity; instead, it restored age-affected kidney epithelial cell thickness.

Conclusions:

  • D-serine supplementation effectively reverses age-associated cognitive decline and brain alterations in rats.
  • Restoring brain D-serine levels presents a potential therapeutic strategy for mitigating aging effects on the brain.