Decrease in age-related tau hyperphosphorylation and cognitive improvement following vitamin D supplementation are associated with modulation of brain energy metabolism and redox state.
Decrease in age-related tau hyperphosphorylation and cognitive improvement following vitamin D supplementation are associated with modulation of brain energy metabolism and redox state.
复制标题
DOI：
10.1016/j.neuroscience.2013.12.064
复制
发表时间：
2014-03-14
期刊：
影响因子：
3.3
通讯作者：
Darwish H
中科院分区：
文献类型：
--
作者：
Briones TL;Darwish H
在本研究中，我们研究了维生素D补充剂是否可以通过增强脑能量稳态和蛋白磷酸酶-2A（PP 2A）活性以及调节氧化还原状态来减少与年龄相关的tau蛋白过度磷酸化和认知障碍。将20个月龄（老年）和6个月龄（年轻）的雄性F344大鼠随机分配至补充维生素D组或不补充维生素D组（对照组）。将大鼠成对饲养，补充组（n=10个年轻和n=10个老年）接受皮下注射维生素D（1，α25-二羟维生素D3）21天。对照动物（N=10只年轻动物和n=10只老年动物）接受等体积的生理盐水，并在维生素D补充开始后第14天开始在水迷宫中进行行为测试。在海马组织中测量Tau磷酸化、脑能量代谢标志物（ADP/ATP比率和腺苷一磷酸活化蛋白激酶）和氧化还原状态（活性氧水平、超氧化物歧化酶活性和谷胱甘肽水平）以及PP 2A活性。我们的研究结果扩展了先前的发现：1）tau蛋白磷酸化在衰老过程中显著增加; 2）大脑能量代谢和氧化还原状态的标志物在衰老过程中显著降低; 3）老年大鼠表现出明显的学习和记忆障碍。更重要的是，我们发现与年龄相关的大脑能量代谢，氧化还原状态和认知功能的变化被维生素D补充剂减弱。未观察到幼龄动物组中tau蛋白过度磷酸化、能量代谢标志物和氧化还原状态的显著差异。我们的数据表明，维生素D通过增强大脑能量代谢、氧化还原状态和PP 2A活性来改善与年龄相关的tau蛋白过度磷酸化和认知能力下降，使其成为缓解衰老影响的潜在有用的治疗选择。
In the present study we examined whether vitamin D supplementation can reduce age-related tau hyperphosphorylation and cognitive impairment by enhancing brain energy homeostasis and protein phosphatase-2A (PP2A) activity, and modulating the redox state. Male F344 rats age 20 months (aged) and 6 months (young) were randomly assigned to either vitamin D supplementation or no supplementation (control). Rats were housed in pairs and the supplementation group (n=10 young and n=10 aged) received subcutaneous injections of vitamin D (1, α25-dihydroxyvitamin D3) for 21 days. Control animals (N=10 young and n=10 aged) received equal volume of normal saline and behavioral testing in water maze started on day 14 after initiation of vitamin D supplementation. Tau phosphorylation, markers of brain energy metabolism (ADP/ATP ratio and adenosine monophosphate-activated protein kinase) and redox state (levels of reactive oxygen species, activity of superoxide dismutase, and glutathione levels) as well as PP2A activity were measured in hippocampal tissues. Our results extended previous findings that: 1) tau phosphorylation significantly increased during aging; 2) markers of brain energy metabolism and redox state are significantly decreased in aging; and 3) aged rats demonstrated significant learning and memory impairment. More importantly, we found that age-related changes in brain energy metabolism, redox state, and cognitive function were attenuated by vitamin D supplementation. No significant differences were seen in tau hyperphosphorylation, markers of energy metabolism and redox state in the young animal groups. Our data suggests that vitamin D ameliorated the age-related tau hyperphosphorylation and cognitive decline by enhancing brain energy metabolism, redox state, and PP2A activity making it a potentially useful therapeutic option to alleviate the effects of aging.
登录
查看更多内容
DOI：
10.1016/j.jsbmb.2006.12.096
发表时间：
2007-03-01
影响因子：
4.1
作者：
Eyles, D.;Almeras, L.;Feron, F.
通讯作者：
Feron, F.
慢性噪音暴露导致大鼠海马和前额叶皮层 Tau 蛋白过度磷酸化持续存在以及 NFT Tau 蛋白的形成
影响因子：
5.3
作者：
Cui, Bo;Zhu, Lixing;Liu, Hongtao
通讯作者：
Liu, Hongtao
影响因子：
4.3
作者：
Fuster-Matanzo A;Llorens-Martín M;Jurado-Arjona J;Avila J;Hernández F
通讯作者：
Hernández F
影响因子：
3.3
作者：
Eyles, D;Brown, J;Feron, F
通讯作者：
Feron, F
影响因子：
4.4
作者：
Federico, Antonio;Cardaioli, Elena;Radi, Elena
通讯作者：
Radi, Elena