MiR-375-3p mediates reduced pineal function in hypoxia-ischemia brain damage
MiR-375-3p mediates reduced pineal function in hypoxia-ischemia brain damage
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MiR-375-3p介导缺氧缺血性脑损伤中松果体功能降低
DOI：
10.1016/j.expneurol.2021.113814
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发表时间：
2021
影响因子：
5.3
通讯作者：
Sun Bin
中科院分区：
文献类型：
--
作者：
Xu Lixiao;Li Gen;Tang Xiaojuan;Feng Chenxi;Li Mei;Jiang Xiaolu;Gu Yan;Yun Yajing;Lu Lianghua;Feng Xing;Din Xin;Sun Bin
MicroRNAs(MiRNAs)在包括缺氧缺血性脑损伤(HIBD)在内的多种疾病中的功能作用已被研究。然而，在HIBD过程中松果体中miRNAs表达的变化和潜在的机制仍不清楚。基于microRNA阵列先前的研究，在HIBD大鼠模型中，数百个miRNAs在松果体中的表达模式发生了变化。在松果体中，miR-375-3p表达显著上调，且表达丰富。对松果体细胞HI体外模型的进一步研究表明，miRNA-375加重了松果体功能的损害。缺氧-葡萄糖剥夺/复氧(OGD/R)后，miR-375-3p表达增加，芳香胺N-乙酰基转移酶(AANAT)表达和褪黑素(MT)分泌减少。在松果体细胞中过表达miRNA-375加重了OGD/R对AANAT表达和MT分泌的影响。由于miRNA-375在松果体细胞中的过表达导致rasd1mRNA和蛋白表达下降，rasd1可能介导miR-375-3p对松果体功能的影响。此外，Morris水迷宫实验显示miR-375-3p加重了HIBD大鼠的认知功能障碍，并影响了HIBD大鼠的情绪和昼夜节律。因此，miR-375-3p可能是HIBD后松果体中的一个关键调节分子，靶向miR-375-3p可能是治疗HIBD的一种新策略。
The functional roles of microRNAs (miRNAs) have been studied in various diseases, including hypoxic-ischemic brain damage (HIBD). However, changes in the expression of miRNAs and the underlying mechanisms in the pineal gland during HIBD remain unknown. Based on the previous study by microRNA array, hundreds of miRNAs showed altered expression patterns in the pineal gland in a rat model of HIBD. MiR-375-3p was found to be significantly upregulated and abundant in the pineal gland. Further investigation in an in vitro HI model of pinealocytes showed that miRNA-375 exacerbated the damage to pineal function. After oxygen-glucose deprivation / reoxygenation (OGD/R), miR-375-3p expression increased, while aralkylamineN-acetyltransferase (AANAT) expression and melatonin (MT) secretion decreased. Overexpression of miRNA-375 in pinealocytes aggravated the influence of OGD/R on AANAT expression and MT secretion. Because miRNA-375 overexpression in pinealocytes induced decreased rasd1 mRNA and protein expression, rasd1 may mediate the effect of miR-375-3p on pineal function. Furthermore, miR-375-3p aggravated the cognitive impairment caused by HIBD in rats, as observed by Morris water maze test, and also affected emotion and circadian rhythm in HIBD-treated rats. Thus, miR-375-3p may be a key regulatory molecule in the pineal gland following HIBD, and targeting of miR-375-3p may represent a new strategy for the treatment of HIBD.