Differential Retinoic Acid Signaling in the Hippocampus of Aged Rats with and without Memory Impairment

Abstract 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 homeostatic synaptic scaling the hippocampus, which supports overall network stability during learning. It been previously determined disrupted signaling hippocampus causes deterioration memory, declines with age brain, application reverses this decline. Here, we explore whether altered an animal model neurocognitive aging. We used Morris water maze protocol study cognitive decline aged rats, assesses hippocampus-dependent spatial memory reveals substantial interindividual differences animals. Aged unimpaired (AU) rats perform on par young (Y), while impaired (AI) animals exhibit deficits. show major substrate for RA, retinol binding protein 4 (RBP4), decreased AU cell surface receptor chronological age. Other affected components include selective increases AI hippocampal synthesis (RALDH1) catabolism (CYP26B1), α, regulated ionotropic glutamate (GluR1), as well fragile X mental retardation (FMRP). The results support conclusion that, surprisingly, increased associated poor outcome.