Age-related effects of ethanol consumption on triiodothyronine and retinoic acid nuclear receptors, neurogranin and neuromodulin expression levels in mouse brain

The effects of ethanol consumption and ageing were investigated on the expression levels of retinoic acid (RA) and triiodothyronine (T3) nuclear receptors (RAR, RXR and TR) and of associated target genes involved in synaptic plasticity, neurogranin (RC3) and neuromodulin (GAP-43) in mice brain. For this purpose, C57BL/6 adult and aged mice were subjected to 5-month ethanol consumption and the mRNA expression of RAR, RXR, TR, RC3 and GAP-43 was measured using a real-time RT-PCR method. GAP-43 and RC3 protein levels also were measured by Western blot. Results showed that 12% ethanol consumption in adult mice (11 months) induced an increase in RARP, RXRP-gamma and TR alpha beta mRNA level in the brain with only an increase in RC3 expression. The same ethanol consumption in aged mice (22 months) reversed the age-related hypo-expression in brain RAR beta, TR alpha beta and target genes RC3 and GAP-43. Compared with our previous behavioral data showing that ethanol is able to partially suppress a selective age-related cognitive deficit, these results suggest that the ethanol-induced increase in RA and T3 nuclear receptors expression could be one of the mechanisms involved in the normalization of synaptic plasticity-associated gene expression altered in aging brain. (c) 2005 Elsevier Inc. All rights reserved.