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摄入益生元(B-GOS)后,大鼠大脑皮层神经元对 NMDA 的反应增强,注意定势转移表现改善。

Increased cortical neuronal responses to NMDA and improved attentional set-shifting performance in rats following prebiotic (B-GOS) ingestion.

机构信息

Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9BH, UK.

4D Pharma, Cornhill Road, Aberdeen AB25 2ZS, UK.

出版信息

Eur Neuropsychopharmacol. 2018 Jan;28(1):211-224. doi: 10.1016/j.euroneuro.2017.11.001. Epub 2017 Nov 22.

Abstract

We have previously shown that prebiotics (dietary fibres that augment the growth of indigenous beneficial gut bacteria) such as Bimuno galacto-oligosaccharides (B-GOS), increased N-methyl-D-aspartate (NMDA) receptor levels in the rat brain. The current investigation examined the functional correlates of these changes in B-GOS-fed rats by measuring cortical neuronal responses to NMDA using in vivo NMDA micro-iontophoresis electrophysiology, and performance in the attentional set-shifting task. Adult male rats were supplemented with B-GOS in the drinking water 3 weeks prior to in vivo iontophoresis or behavioural testing. Cortical neuronal responses to NMDA iontophoresis, were greater (+30%) in B-GOS administered rats compared to non-supplemented controls. The intake of B-GOS also partially hindered the reduction of NMDA responses by the glycine site antagonist, HA-966. In the attentional set-shifting task, B-GOS -fed rats shifted from an intra-dimensional to an extra-dimensional set in fewer trials than controls, thereby indicating greater cognitive flexibility. An initial exploration into the mechanisms revealed that rats ingesting B-GOS had increased levels of plasma acetate, and cortical GluN2B subunits and Acetyl Co-A Carboxylase mRNA. These changes were also observed in rats fed daily for 3 weeks with glyceryl triacetate, though unlike B-GOS, cortical histone deacetylase (HDAC1, HDAC2) mRNAs were also increased which suggested an additional epigenetic action of direct acetate supplementation. Our data demonstrate that a pro-cognitive effect of B-GOS intake in rats is associated with an increase in cortical NMDA receptor function, but the role of circulating acetate derived from gut bacterial fermentation of this prebiotic requires further investigation.

摘要

我们之前已经表明,某些益生元(可促进肠道内有益细菌生长的膳食纤维),如双糖乳杆菌(B-GOS)可增加大鼠大脑中的 N-甲基-D-天冬氨酸(NMDA)受体水平。目前的研究通过使用体内 NMDA 微电泳电生理学和注意力转换任务来测量皮质神经元对 NMDA 的反应,来检测 B-GOS 喂养大鼠中这些变化的功能相关性。成年雄性大鼠在体内离子电泳或行为测试前 3 周在饮用水中补充 B-GOS。与未补充对照相比,B-GOS 给药大鼠的 NMDA 离子电泳皮质神经元反应增加(+30%)。B-GOS 的摄入也部分阻碍了甘氨酸位点拮抗剂 HA-966 对 NMDA 反应的降低。在注意力转换任务中,B-GOS 喂养的大鼠在较少的试验中从内维度转换为外维度,表明认知灵活性更高。对机制的初步探索表明,摄入 B-GOS 的大鼠血浆乙酸盐水平以及皮质 GluN2B 亚基和乙酰辅酶 A 羧化酶 mRNA 水平增加。在连续 3 周每天喂食甘油三乙酸酯的大鼠中也观察到这些变化,但与 B-GOS 不同,皮质组蛋白去乙酰化酶(HDAC1、HDAC2)mRNA 也增加,这表明直接补充乙酸盐具有额外的表观遗传作用。我们的数据表明,B-GOS 摄入对大鼠的认知促进作用与皮质 NMDA 受体功能的增加有关,但需要进一步研究源自肠道细菌发酵这种益生元的循环乙酸盐的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0945/5857269/d9389a295efb/gr1.jpg

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