Differential retinoic acid signaling in the hippocampus of aged rats with and without memory impairment

Marta U. Wołoszynowska-Fraser, Sharyn L. Rossi, Jeffrey M. Long, Peter J. McCaffery, Peter R. Rapp*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
7 Downloads (Pure)


Retinoic acid (RA), a metabolite of vitamin A, has many physiological functions, and mounting evidence points to important roles in cognition. In vitro experiments indicate that RA is involved in homeostatic synaptic scal-ing in the hippocampus, which supports overall network stability during learning. It has been previously determined that disrupted RA signaling in the hippocampus causes deterioration of memory, that RA signaling declines with age in brain, and that application of RA reverses this decline. Here, we explore whether RA signaling is altered in an animal model of neurocognitive aging. We used a Morris water maze protocol to study cognitive decline in aged rats, which assesses hippocampus-dependent spatial memory and reveals substan-tial interindividual differences in aged animals. Aged unimpaired (AU) rats perform on par with young (Y), while aged impaired (AI) animals exhibit spatial memory deficits. We show that the major substrate for RA, retinol binding protein 4 (RBP4), is decreased in AU rats, and retinol cell surface receptor declines with chronological age. Other affected components of RA signaling include selective increases in AI animals in hippocampal synthesis (RALDH1) and catabolism of RA (CYP26B1), RA receptor a, the RA regulated ionotropic glutamate receptor (GluR1), as well as fragile X mental retardation protein (FMRP). The results support the conclusion that, surprisingly, increased RA signaling in the aged hippocampus is associated with poor cognitive outcome.

Original languageEnglish
Article numberENEURO.0120-21.2021
Number of pages14
Issue number5
Early online date20 Aug 2021
Publication statusPublished - 30 Sept 2021

Bibliographical note

Funding Information:
This work was entirely supported by the Intramural Research Program of the National Institutes of Health, National institute on Aging.


  • Aging
  • Hippocampus
  • Memory
  • Retinoic acid
  • Spatial
  • Vitamin A


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