打工人「救命水」实锤!JCI:长期喝咖啡,能改善大脑代谢,提高记忆力和学习力!

2022-08-06 Swagpp MedSci原创

JCI:习惯性咖啡因消耗会从表观基因组、蛋白质组、代谢组学等多水平上对海马体产生影响,从而提升认知能力,增强记忆力和学习效果。换句话说,天天喝咖啡,真的会改变大脑,不过是往更好的方向!

清晨醒来冲上一杯咖啡,在馥郁的满室醇香中开启新一天的学习,仿佛更能沉心于其中;昏黄的灯光、来往的路人、手边的咖啡,更能给独自斜坐在咖啡馆一角的作家带去一丝创作的灵感;林立的办公楼中,从周一到周五永远都充斥着咖啡的香气,伴随着的是更的工作效率......

一直以来,咖啡以其“强大提神”的功效风靡全球——能让人在短时间内赶走“瞌睡虫”,从而集中精力完成手上的工作。慢慢地,咖啡成为很多人生活中不可或缺的一部分,更被当代打工人亲切地称为“续命神器”。

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图源:网络 

然而,长期饮用咖啡的打工人是否有过这样的担心:天天喝咖啡会不会提前“透支”脑子而使人变笨?在长期来看,咖啡的“提神功能”是否会对大脑产生影响呢?

为了回答这个问题,法国的研究学者以小鼠为研究模型,探究长期摄入咖啡对于大脑中的分子及信号通路的影响。结果显示,习惯性咖啡因消耗会从表观基因组、蛋白质组、代谢组学等多水平上对海马体产生影响,从而提升认知能力,增强记忆力和学习效果。换句话说,天天喝咖啡,真的会改变大脑,不过是往更好的方向!该研究发表在临床研究杂志JCI(The Journal of Clinical Investigation)上。

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DOI: 10.1172/JCI149371

研究者使用0.3g/L的口服咖啡因溶液喂养小鼠,平均消耗量为4.83±0.15mL,确保小鼠每天摄入1.45mg左右咖啡因,并持续2周,来模拟人类长期摄入咖啡因的通常剂量范围(≈每天2-4杯市售咖啡)

在该浓度的咖啡因喂养下,研究者检测到小鼠脑内的咖啡因浓度为3.6±1.1μM,以及咖啡因代谢物副黄嘌呤、可可碱和茶碱,脑内的浓度分别为1.9±0.4μM、1.8±0.3μM和0.10±0.03μM。

看来,“喝咖啡上头”真不是句玩笑话~

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研究过程

研究结果显示:长期摄入咖啡因会从表观基因组(A)、代谢组(B)、蛋白质组(C)三方面改变小鼠海马,实现“一马三改”。

A. 长期摄入咖啡因会影响小鼠海马的表观基因组

研究者发现,长期的咖啡因摄入可以显著降低小鼠脑内的多个基因点位中组蛋白的乙酰化水平,而这些基因与各种代谢过程有着密切的联系,尤其是葡萄糖和脂质代谢。

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长期咖啡因摄入对表观基因组的改变

B. 长期摄入咖啡因会影响小鼠海马的代谢组

研究者使用基质辅助激光解析电离质谱成像法(MALDI-MSI)进一步评估了组蛋白乙酰化降低对海马代谢组的影响。统计分析表明,长期摄入咖啡因导致代谢物和脂质水平大幅下降,即92%的大脑内代谢相关分子水平出现了下降趋势,仅有8%出现升高。这意味着,咖啡因的摄入显著改变了海马代谢过程。

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长期咖啡因摄入对代谢组的改变

C. 长期摄入咖啡因会影响小鼠海马的蛋白质组

为了深入了解慢性咖啡因摄入在蛋白质水平上的潜在影响,研究者对实验组和对照组小鼠的背侧海马进行了MS蛋白质组学分析。与对照组相比,咖啡因导致179种蛋白质改变,其中有49种蛋白表达水平降低,130种升高。与表观基因组学和代谢组学的结果一致,表达降低的49种蛋白质与脂质代谢以及线粒体有关。

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长期咖啡因摄入对蛋白质组的改变

以上三种方法表明,慢性咖啡因很大程度上导致海马组织的代谢改变,包括蛋白质翻译、脂质代谢和胰岛素相关的代谢过程。(说人话就是),长期摄入咖啡因确实可以改变大脑。

然而,仅停留在代谢层面也太“虚无缥缈”了吧!这些代谢上的改变,具体产生了怎样的影响呢?

在对这130种变化的蛋白质进行分析后,研究者发现:长期咖啡因摄入通过影响基因表达,对与海马神经元的突触传递和可塑性过程相关的蛋白质有着正表观遗传调节作用,甚至部分变化表现出长效影响。

具体到小鼠的表现上,研究者使用Morris水迷宫对小鼠进行为期3天的空间记忆训练,对比咖啡因摄入情况对小鼠的记忆力和学习能力的影响。

结果显示,虽然两组小鼠有着相似的平均游泳速度,但摄入咖啡因的小鼠组表现出更高的位置熟悉度,也能使用更少的时间“逃出迷宫”。进一步对海马体的RNA-Seq分析也展现,在学习了一项任务后,咖啡因使得与记忆形成的基因表达更为活跃。

也就是说,长期的咖啡摄入,能有效增加突触相关蛋白水平,提高小鼠的记忆力和学习能力,从而提升认知功能!看来小编学习成绩不好,完全是以前咖啡喝得不够多啊......

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小鼠训练实验情况对比

但读者们往往有这样的疑惑:上述研究不过是基于动物实验,真的能推广到人吗?长期喝咖啡会对人类大脑有怎样的影响?

事实上,Nature子刊Molecular Psychiatry期刊上发表的一项研究,就使用功能磁共振成像(fMRI)技术对比了经常喝咖啡和不喝咖啡的人在休息、工作、喝咖啡之后的大脑结构和连接情况,也得到了类似的结果。

与不喝咖啡的人相比,经常喝咖啡使得人脑中个别区域之间出现了更有效的连接模式和动态活动的增加,提示运动控制能力的增加和专注能力的提高。

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https://doi.org/10.1038/s41380-021-01075-4

看来,咖啡不仅能续命,甚至能改造大脑,使人“变聪明”!我喝的哪里是咖啡,我喝的是“脑白金”啊~

 

参考文献:

[1]Paiva I, Cellai L, Meriaux C, Poncelet L, Nebie O, Saliou JM, Lacoste AS, Papegaey A, Drobecq H, Le Gras S, Schneider M, Malik EM, Müller CE, Faivre E, Carvalho K, Gomez-Murcia V, Vieau D, Thiroux B, Eddarkaoui S, Lebouvier T, Schueller E, Tzeplaeff L, Grgurina I, Seguin J, Stauber J, Lopes LV, Buée L, Buée-Scherrer V, Cunha RA, Ait-Belkacem R, Sergeant N, Annicotte JS, Boutillier AL, Blum D. Caffeine intake exerts dual genome-wide effects on hippocampal metabolism and learning-dependent transcription. J Clin Invest. 2022 Jun 15;132(12):e149371. doi: 10.1172/JCI149371. PMID: 35536645; PMCID: PMC9197525.
[2]Magalhães, R., Picó-Pérez, M., Esteves, M. et al. Habitual coffee drinkers display a distinct pattern of brain functional connectivity. Mol Psychiatry 26, 6589–6598 (2021). https://doi.org/10.1038/s41380-021-01075-4

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    2022-08-06 ms1000000797884897

    高度同意哦

    0

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    2022-08-06 追寻2008

    学习了,以后多喝咖啡

    0

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    2022-08-06 weigq

    广告???

    0

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