Estrogen and exercise interact to regulate brain-derived neurotrophic factor mRNA and protein expression in the hippocampus
Estrogen and exercise interact to regulate brain-derived neurotrophic factor mRNA and protein expression in the hippocampus
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DOI：
10.1046/j.0953-816x.2001.01825.x
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发表时间：
2001-12-01
影响因子：
3.4
通讯作者：
Cotman, CW
中科院分区：
文献类型：
--
作者：
Berchtold, NC;Kesslak, JP;Cotman, CW
我们研究了雌激素和运动在海马区相互作用并调节脑源性神经营养因子(BDNF)的可能性，BDNF是一种越来越多地被认为在可塑性和神经元功能中发挥作用的分子。本研究的一个重要方面是考察雌激素丢失和雌激素替代干预之间的不同时间间隔的影响。我们证明，在完整的雌性大鼠中，体育活动增加了海马区BDNF的mRNA和蛋白水平。然而，在没有雌激素的情况下，运动对BDNF上调的影响会以一种时间依赖的方式降低。此外，自愿活动本身也受到雌激素的刺激。在运动动物中，剥夺雌激素降低了自愿活动水平，而雌激素替代使活动恢复到正常水平。在久坐不动的动物中，雌激素剥夺(卵巢切除)降低了基线BDNF的mRNA和蛋白，而这些基因和蛋白可以通过雌激素替代来恢复。尽管在去卵巢的情况下，运动降低了活动水平，但短期(3周)雌激素剥夺后，运动增加了海马区BDNF mRNA的水平。然而，长期剥夺雌激素会削弱锻炼的效果。在剥夺雌激素7周后，单独运动不再影响脑源性神经营养因子的mRNA或蛋白水平。然而，运动联合长期雌激素替代增加BDNF蛋白的效果高于单独补充雌激素的效果。有趣的是，所有条件下的蛋白质水平与齿状回的mRNA水平关系最为密切，这表明该海马区的mRNA表达可能是海马BDNF蛋白库的主要贡献者。雌激素、体力活动和海马区BDNF的相互作用可能是维持大脑健康、可塑性和整体幸福感的重要问题，特别是在女性。
We investigated the possibility that estrogen and exercise interact in the hippocampus and regulate brain-derived neurotrophic factor (BDNF), a molecule increasingly recognized for its role in plasticity and neuron function. An important aspect of this study is to examine the effect of different time intervals between estrogen loss and estrogen replacement intervention. We demonstrate that in the intact female rat, physical activity increases hippocampal BDNF mRNA and protein levels. However, the exercise effect on BDNF up-regulation is reduced in the absence of estrogen, in a time-dependent manner. In addition, voluntary activity itself is stimulated by the presence of estrogen. In exercising animals, estrogen deprivation reduced voluntary activity levels, while estrogen replacement restored activity to normal levels. In sedentary animals, estrogen deprivation (ovariectomy) decreased baseline BDNF mRNA and protein, which were restored by estrogen replacement. Despite reduced activity levels in the ovariectomized condition, exercise increased BDNF mRNA levels in the hippocampus after short-term (3 weeks) estrogen deprivation. However, long-term estrogen-deprivation blunted the exercise effect. After 7 weeks of estrogen deprivation, exercise alone no longer affected either BDNF mRNA or protein levels. However, exercise in combination with long-term estrogen replacement increased BDNF protein above the effects of estrogen replacement alone. Interestingly, protein levels across all conditions correlated most closely with mRNA levels in the dentate gyrus, suggesting that expression of mRNA in this hippocampal region may be the major contributor to the hippocampal BDNF protein pool. The interaction of estrogen, physical activity and hippocampal BDNF is likely to be an important issue for maintenance of brain health, plasticity and general wellbeing, particularly in women.