Boucheron Catherine, Alfos Serge, Enderlin Valérie, Husson Marianne, Pallet Véronique, Jaffard Robert, Higueret Paul
Unité de Nutrition et Signalisation Cellulaire, EA MENRT; USC INRA, ISTAB, Université Bordeaux 1, 33405 Talence Cedex, France.
Neurobiol Aging. 2006 Sep;27(9):1326-34. doi: 10.1016/j.neurobiolaging.2005.07.008. Epub 2005 Aug 22.
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 RARbeta, RXRbetagamma and TRalphabeta 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 RARbeta, TRalphabeta 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.
研究了乙醇摄入和衰老对小鼠脑中视黄酸（RA）和三碘甲状腺原氨酸（T3）核受体（RAR、RXR和TR）以及参与突触可塑性的相关靶基因神经颗粒素（RC3）和神经调节蛋白（GAP-43）表达水平的影响。为此，将C57BL/6成年和老年小鼠进行为期5个月的乙醇摄入，并用实时RT-PCR方法检测RAR、RXR、TR、RC3和GAP-43的mRNA表达。还通过蛋白质印迹法检测了GAP-43和RC3的蛋白水平。结果显示，成年小鼠（11个月）摄入12%乙醇可诱导脑中RARβ、RXRβγ和TRαβ的mRNA水平升高，且仅RC3表达增加。老年小鼠（22个月）摄入相同量的乙醇可逆转脑中RARβ、TRαβ以及靶基因RC3和GAP-43与年龄相关的低表达。与我们之前的行为学数据表明乙醇能够部分抑制与年龄相关的选择性认知缺陷相比，这些结果表明乙醇诱导的RA和T3核受体表达增加可能是参与衰老大脑中突触可塑性相关基因表达正常化的机制之一。
