Age-related decreases in mRNA for brain nuclear receptors and target genes are reversed by retinoic acid treatment

Ageing is accompanied by certain problems resulting from changes of hormonal status, in particular thyroid hormone (T 3) status and vitamin A status. Since retinoic acid (RA), the active metabolite of vitamin A, and T 3 play physiological roles in the adult brain, the effect of ageing on the amounts of mRNA for retinoic acid (RAR and RXR) and triiodothyronine (TR) nuclear receptors were studied. Also, the expression of RA and T 3 target genes, tissue transglutaminase (tTG) and neurogranin (RC3), was measured in the whole brain and in the hippocampus of mice. Relative to young (3 months) mice, aged (22 months) mice exhibited lower amounts of RAR, RXR and TR mRNA concomitantly with a lower expression of tTG and RC3. RA administration to old mice (24 h before sacrifice) was able to restore the amount of mRNA of nuclear receptors and of RC3. It is hypothesized that a decrease in the cellular action of RA and T 3 could play a role, via a decrease in the expression of RC3, in the alteration of synaptic plasticity occurring in aged mice.