补充谷氨酰胺改善了小鼠前额叶皮层中谷氨酸和谷氨酰胺转运蛋白的慢性应激诱导的减少。,Experimental Neurobiology

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补充谷氨酰胺改善了小鼠前额叶皮层中谷氨酸和谷氨酰胺转运蛋白的慢性应激诱导的减少。
Experimental Neurobiology ( IF 1.8 ) Pub Date : 2019-04-30 , DOI: 10.5607/en.2019.28.2.270
Ji Hyeong Baek ₁ , Arul Vignesh ₁ , Hyeonwi Son ₁ , Dong Hoon Lee ₁ , Gu Seob Roh ₁ , Sang Soo Kang ₁ , Gyeong Jae Cho ₁ , Wan Sung Choi ₁ , Hyun Joon Kim ₁

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慢性固定应激（CIS）会在小鼠前额叶皮层（PFC）中诱导低水平的谷氨酸（Glu）和谷氨酰胺（Gln）以及谷氨酸能亢进信号传导，这与Glu-Gln循环密切相关。补充Gln的饮食可改善CIS引起的有害变化。在这里，我们调查了CIS和Gln补充对Glu-Gln循环相关蛋白的影响，以表征其潜在机制。使用CIS诱导的抑郁小鼠模型，我们检查了PFC中Glu-Gln循环中11种蛋白质的表达。CIS降低了谷氨酸转运蛋白1（GLT1）和钠偶联中性氨基酸转运蛋白（SNAT）1，SANT2，SNAT3和SNAT5的水平。补充Gln不会影响非应激组，但会显着增加应激组的GLT1和SNAT。通过免疫组织化学分析，我们证实，应激组内侧PFC的神经元中SNAT1和SNAT2减少，星形胶质细胞中GLT1，SNAT3和SNAT5减少，但是补充Gln的饮食改善了这些减少。总体而言，这些结果表明，CIS可能通过减少PFC中的Glu和Gln转运而引起类似抑郁的行为，补充Gln的饮食可以防止CIS的有害作用。

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Glutamine Supplementation Ameliorates Chronic Stress-induced Reductions in Glutamate and Glutamine Transporters in the Mouse Prefrontal Cortex.

Chronic immobilization stress (CIS) induces low levels of glutamate (Glu) and glutamine (Gln) and hypoactive glutamatergic signaling in the mouse prefrontal cortex (PFC), which is closely related to the Glu-Gln cycle. A Gln-supplemented diet ameliorates CIS-induced deleterious changes. Here, we investigated the effects of CIS and Gln supplementation on Glu-Gln cycle-related proteins to characterize the underlying mechanisms. Using the CIS-induced depression mouse model, we examined the expression of 11 proteins involved in the Glu-Gln cycle in the PFC. CIS decreased levels of glutamate transporter 1 (GLT1) and sodium-coupled neutral amino acid transporter (SNAT) 1, SANT2, SNAT3, and SNAT5. Gln supplementation did not affect the non-stressed group but significantly increased GLT1 and SNATs of the stressed group. By immunohistochemical analysis, we confirmed that SNAT1 and SNAT2 were decreased in neurons and GLT1, SNAT3, and SNAT5 were decreased in astrocytes in the medial PFC of the stressed group, but Gln-supplemented diet ameliorated these decrements. Collectively, these results suggest that CIS may cause depressive-like behaviors by decreasing Glu and Gln transportation in the PFC and that a Gln-supplemented diet could prevent the deleterious effects of CIS.

更新日期：2020-08-21

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