Wan Lijia, He Xiaori, He Mingfeng, Yu Yuanqiang, Jiang Weiming, Liang Can, Luo Kaiju, Gong Xiaoyun, Yang Yonghui, Dong Qingyi, Chen Pingyang
Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
Department of Child Healthcare, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan 410011, PR China.
Heliyon. 2023 Jan 27;9(2):e12920. doi: 10.1016/j.heliyon.2023.e12920. eCollection 2023 Feb.
Intrauterine growth restriction (IUGR) is defined as the failure of a fetus to reach its genetic growth potential in utero resulted by maternal, placental, fetal, and genetic factors. Previous studies have reported that IUGR is associated with a high incidence of neurological damage, although the precise causes of such damage remain unclear. We aimed to investigate whether cognitive impairment in rats with IUGR is related to pyroptosis of hippocampal neurons and determine the effect of early intervention with docosahexaenoic acid (DHA).
Learning and memory function was assessed using the Morris water maze test. The morphological structure and ultrastructure of the hippocampus was examined via hematoxylin and eosin staining and electron microscopy respectively. The pyroptosis of hippocampal neuron was detected by gasdermin-D (GSDMD) immunofluorescence staining, mRNA and protein expression of nuclear localization leucine-rich-repeat protein 1 (NLRP1), caspase-1, GSDMD, and quantification of inflammatory cytokines interleukin (IL)-1β and IL-18 in the hippocampus.
IUGR rats exhibited decreased learning and memory function, morphological structure and ultrastructural changes in hippocampus compared to controls. IUGR rats also exhibited increased hippocampal quantification of GSDMD immunofluorescence staining, increased mRNA and protein expression of NLRP1, caspase-1, and GSDMD, and increased quantification of IL-1β and IL-18 in the hippocampus. Intervention with DHA attenuated these effects.
Cognitive impairment in rats with IUGR may be related to pyroptosis of hippocampal neurons. Early intervention with DHA may attenuate cognitive impairment and reduce hippocampal pyroptosis in rats with IUGR.
宫内生长受限(IUGR)被定义为胎儿由于母体、胎盘、胎儿及遗传因素而未能在子宫内实现其遗传生长潜力。既往研究报道,IUGR与神经损伤的高发生率相关,尽管此类损伤的确切原因仍不清楚。我们旨在研究IUGR大鼠的认知障碍是否与海马神经元的焦亡有关,并确定二十二碳六烯酸(DHA)早期干预的效果。
采用莫里斯水迷宫试验评估学习和记忆功能。分别通过苏木精-伊红染色和电子显微镜检查海马的形态结构和超微结构。通过gasdermin-D(GSDMD)免疫荧光染色、富含亮氨酸重复序列蛋白1(NLRP1)、半胱天冬酶-1、GSDMD的mRNA和蛋白表达以及海马中炎性细胞因子白细胞介素(IL)-1β和IL-18的定量检测海马神经元的焦亡。
与对照组相比,IUGR大鼠表现出学习和记忆功能下降、海马形态结构和超微结构改变。IUGR大鼠海马中GSDMD免疫荧光染色定量增加、NLRP1、半胱天冬酶-1和GSDMD的mRNA和蛋白表达增加,海马中IL-1β和IL-18的定量增加。DHA干预减弱了这些作用。
IUGR大鼠的认知障碍可能与海马神经元的焦亡有关。DHA早期干预可能减轻IUGR大鼠的认知障碍并减少海马焦亡。