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

Age-related effects of ethanol consumption on triiodothyronine and retinoic acid nuclear receptors, neurogranin and neuromodulin expression levels in mouse brain
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DOI:
10.1016/j.neurobiolaging.2005.07.008
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发表时间:
2006-09-01
影响因子:
4.2
通讯作者:
Higueret, Paul
Higueret, Paul
中科院分区:
医学2区
文献类型:
--
作者:
Boucheron, Catherine;Alfos, Serge;Higueret, Paul

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研究了乙醇消耗和衰老对小鼠大脑中视黄酸(RA)和三碘甲状腺原氨酸(T3)核受体(RAR、RXR和TR)以及涉及突触可塑性、神经颗粒素(RC3)和神经调节蛋白(GAP-43)的相关靶基因表达水平的影响。为此,对 C57BL/6 成年和老年小鼠进行 5 个月的乙醇消耗,并使用实时 RT-PCR 方法测量 RAR、RXR、TR、RC3 和 GAP-43 的 mRNA 表达。还通过蛋白质印迹测量了 GAP-43 和 RC3 蛋白水平。结果显示,成年小鼠(11 个月)摄入 12% 乙醇会导致大脑中 RARP、RXRP-gamma 和 TR αβ mRNA 水平增加,而仅 RC3 表达增加。老年小鼠(22 个月)摄入相同的乙醇可逆转大脑 RAR β、TR α β 以及靶基因 RC3 和 GAP-43 中与年龄相关的低表达。与我们之前显示乙醇能够部分抑制选择性年龄相关认知缺陷的行为数据相比,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改变正常化的机制之一。 (c) 2005 Elsevier Inc. 保留所有权利。
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.