Retinoic acid reverses the PTU related decrease in neurogranin level in mice brain

Recent data have shown that fine regulation of retinoid mediated gene expression is fundamentally important for optimal brain functioning in aged mice. Nevertheless, alteration of the thyroid hormone signalling pathway may be a limiting factor, which impedes retinoic acid (RA) from exerting its modulating effect. Mild hypothyroidism is often described in the elderly. Thus, in the present study, it was of interest to determine if RA exerts its neurological modulating effect in mild hypothyroidism. To obtain further insight into this question, mice were submitted to a low propylthiouracyl (PTU) drink (0.05%) in order to slightly reduce the serum level of triiodothyronine (T3). A quantitative evaluation of RA nuclear receptors (RAR, RXR), T3 nuclear receptor (TR) and of neurogranin (RC3, a RA target gene which codes for a protein considered as a good marker of synaptic plasticity) in PTU treated mice injected with vehicle or RA or T3 was carried out. The PTU-related decrease in expression of RAR, RXR and RC3 was restored following RA or T3 administration, as observed in aged mice. The amount of TR mRNA, which was not affected in PTU treated mice, was increased only after T3 treatment as observed in overt hypothyroidism. These results suggest that neurobiological alterations observed in aged mice are probably related to RA and T3 signalling pathway modifications associated, in part, with mild changes in thyroid function.