Wnt pathway regulation by long-term moderate exercise in rat hippocampus

Wnt pathway regulation by long-term moderate exercise in rat hippocampus
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DOI:
10.1016/j.brainres.2013.10.048
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发表时间:
2014-01-16
期刊:
影响因子:
2.9
通讯作者:
Canudas, A. M.
Canudas, A. M.
中科院分区:
医学3区
文献类型:
--
作者:
Bayod, S.;Menella, I.;Canudas, A. M.

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一个积极的生活方式,包括定期锻炼,减少了衰老过程的有害影响。在大脑水平,突触可塑性和神经发生都受到运动的调节,尽管这些作用的分子机制还不清楚。在成熟的神经系统中,经典Wnt(Wnt/β-连环蛋白)信号通路涉及神经保护和突触可塑性。在这里,我们研究了Wnt通路是否可以调制成年雄性大鼠海马长期适度运动(跑步机运行)或丰富(处理/环境刺激)。久坐不动的动物表现出更高的Wnt拮抗剂Dkk-1蛋白水平,运动组中的水平最低。虽然没有证据表明LRP 6受体的活化发生了任何变化,但在运动和富集的动物中,LRP 6的总水平较高。对参与β-连环蛋白磷酸化(最终导致其蛋白酶体降解)的一些组分的分析显示,在久坐动物中Axin 1和GSK-3 α/β的水平和活化分别较高。然而,实验组之间的不同磷酸化形式和总β-连环蛋白水平均无差异。较高的蛋白水平Axin 2和抗凋亡蛋白Bcl-2,发现与运动和处理,而proapototic,Bax,不受影响。因此,我们的研究结果表明,Wnt通路的激活不仅与适度的运动,而且与动物的处理。(C)2013爱思唯尔有限公司版权所有。
An active lifestyle involving regular exercise reduces the deleterious effects of the aging process. At the cerebral level, both synaptic plasticity and neurogenesis are modulated by exercise, although the molecular mechanisms underlying these effects are not clearly understood. In the mature nervous system, the canonical Wnt (Wnt/beta-catenin) signaling pathway is implicated in neuroprotection and synaptic plasticity. Here, we examined whether the Wnt pathway could be modulated in adult male rat hippocampus by long-term moderate exercise (treadmill running) or enrichment (handling/environmental stimulation). Sedentary animals showed higher protein levels of the Wnt antagonist, Dkk-1, the lowest levels being found in the exercised group. Although there was no evidence of any changes in activation of the LRP6 receptor, the total levels of LRP6 were higher in exercised and enriched animals. Analysis of some of the components implicated in the phosphorylation of p-catenin, which leads ultimately to its proteasomal degradation, revealed higher levels and activation of Axin1 and GSK-3 alpha/beta respectively in sedentary animals. However neither different phosphorylated forms nor total p-catenin protein levels differed between the experimental groups. Higher protein levels of Axin2 and the antiapoptotic protein, Bcl-2, were found with exercise and handling, whereas the proapototic, Bax, was unaffected. Thus, our results suggest activation of the Wnt pathway not only with moderate exercise, but also with the handling of the animals. (C) 2013 Elsevier B.V. All rights reserved.