Sulforaphane Increase Mitochondrial Biogenesis-Related Gene Expression in the Hippocampus and Suppresses Age-Related Cognitive Decline in Mice.

Sulforaphane Increase Mitochondrial Biogenesis-Related Gene Expression in the Hippocampus and Suppresses Age-Related Cognitive Decline in Mice.
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萝卜硫素增加小鼠海马区线粒体生物发生相关基因的表达并抑制与年龄相关的认知能力下降。

DOI:
10.3390/ijms23158433
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发表时间:
2022-07-29
影响因子:
5.6
通讯作者:
Itoh, Ken
Itoh, Ken
中科院分区:
生物学2区
文献类型:
--
作者:
Shimizu, Sunao;Kasai, Shuya;Yamazaki, Hiromi;Tatara, Yota;Mimura, Junsei;Engler, Mate Janos;Tanji, Kunikazu;Nikaido, Yoshikazu;Inoue, Takuro;Suganuma, Hiroyuki;Wakabayashi, Koichi;Itoh, Ken

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萝卜硫素(SFN)是转录因子核因子红系2 (NF-E2)相关因子2 (NRF2)的有效激活剂。SFN及其前体硫代葡萄糖苷(sulforapane glucosinolate, SGS)在临床试验和体内研究中已被证明可以改善认知功能。然而,SGS对衰老加速小鼠8 (SAMP8)中与年龄相关的认知能力下降的影响尚不清楚。在这项研究中,我们确定了SGS对年龄相关认知能力下降的预防潜力。1月龄SAMP8小鼠和对照SAMR1小鼠分别饲喂含有或不含SGS的花椰菜芽粉(日粮中SGS含量为0.3%)的随意饲粮,直至13月龄。SGS显著改善了SAMP8在12月龄时的长期记忆。有趣的是,在13月龄的SAMR1和SAMP8中,SGS增加了海马过氧化物酶体增殖体激活受体γ辅助激活因子-1 α (PGC1α)和线粒体转录因子A (TFAM)的mRNA和蛋白水平,这是线粒体生物发生的主要调节因子。此外,SAMP8小鼠的核呼吸因子-1 (NRF-1)和线粒体DNA编码的呼吸复合体酶的mrna增加,但线粒体DNA本身没有增加。这些结果表明,SGS通过维持衰老加速小鼠的线粒体功能来预防与年龄相关的认知能力下降。
Sulforaphane (SFN) is a potent activator of the transcriptional factor, Nuclear Factor Erythroid 2 (NF-E2)-Related factor 2 (NRF2). SFN and its precursor, glucoraphanin (sulforaphane glucosinolate, SGS), have been shown to ameliorate cognitive function in clinical trials and in vivo studies. However, the effects of SGS on age-related cognitive decline in Senescence-Accelerated Mouse Prone 8 (SAMP8) is unknown. In this study, we determined the preventive potential of SGS on age-related cognitive decline. One-month old SAMP8 mice or control SAM resistance 1 (SAMR1) mice were fed an ad libitum diet with or without SGS-containing broccoli sprout powder (0.3% w/w SGS in diet) until 13 months of age. SGS significantly improved long-term memory in SAMP8 at 12 months of age. Interestingly, SGS increased hippocampal mRNA and protein levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α) and mitochondrial transcription factor A (TFAM), which are master regulators of mitochondrial biogenesis, both in SAMR1 and SAMP8 at 13 months of age. Furthermore, mRNAs for nuclear respiratory factor-1 (NRF-1) and mitochondrial DNA-encoded respiratory complex enzymes, but not mitochondrial DNA itself, were increased by SGS in SAMP8 mice. These results suggest that SGS prevents age-related cognitive decline by maintaining mitochondrial function in senescence-accelerated mice.
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