Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou 215000, China.
Department of Neonatology, Children's Hospital of Soochow University, Suzhou 215000, China.
Exp Neurol. 2021 Oct;344:113814. doi: 10.1016/j.expneurol.2021.113814. Epub 2021 Jul 17.
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 aralkylamine N-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.
微小 RNA（miRNAs）的功能作用已在多种疾病中进行了研究，包括缺氧缺血性脑损伤（HIBD）。然而，HIBD 期间松果体中 miRNAs 的表达变化及其潜在机制尚不清楚。基于 miRNA 芯片的先前研究，在 HIBD 大鼠模型中，数百种 miRNAs 在松果体中表现出改变的表达模式。miR-375-3p 被发现显著上调且在松果体中含量丰富。在松果体细胞的体外 HI 模型中的进一步研究表明，miRNA-375 加剧了对松果体功能的损伤。在氧葡萄糖剥夺/复氧（OGD/R）后，miR-375-3p 的表达增加，而芳香族胺 N-乙酰转移酶（AANAT）的表达和褪黑素（MT）分泌减少。松果体细胞中 miRNA-375 的过表达加剧了 OGD/R 对 AANAT 表达和 MT 分泌的影响。因为松果体细胞中 miRNA-375 的过表达导致 rasd1 mRNA 和蛋白表达降低，rasd1 可能介导了 miR-375-3p 对松果体功能的影响。此外，miR-375-3p 通过 Morris 水迷宫试验加重了 HIBD 大鼠引起的认知障碍，并且还影响了 HIBD 治疗大鼠的情绪和昼夜节律。因此，miR-375-3p 可能是 HIBD 后松果体中的关键调节分子，针对 miR-375-3p 可能代表 HIBD 治疗的新策略。
