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子痫前期 N-硝基-L-精氨酸甲酯大鼠模型中少突胶质细胞死亡导致感觉运动和认知功能缺陷。

Oligodendrocytes Death Induced Sensorimotor and Cognitive Deficit in N-nitro-L-arginine methyl Rat Model of Pre-eclampsia.

机构信息

Optics and Imaging Centre, Doris Duke Medical Research Institute, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.

出版信息

Neurochem Res. 2020 Apr;45(4):902-914. doi: 10.1007/s11064-020-02969-5. Epub 2020 Jan 25.

Abstract

Pre-eclampsia (PE) is a pregnancy complicated syndrome that affects multiple organs including the brain that continue post- delivery in both mother and the offspring. We evaluated the expression of oligodendrocytes in the brain of PE rat model through development as well as the cognitive changes and other behavioural modifications that may occur later in the life of offspring of PE-like rat model. Pregnant rats divided into early-onset and late-onset groups were administered with N-nitro- L-arginine methyl (L-NAME) through drinking water at gestational days (GD) 8-17. Rats were allowed free access to water throughout the pregnancy. At GD 19, post-natal day (PND) 1 and 60, rats were sacrificed and brain excised for further analysis. The offspring were subjected to behavioural studies for cognitive and sensorimotor impairments before sacrificed at PND 60. Results showed significant down-regulation in the expression of OLIG2 in PE at GD 19 brain which persists till PND 60. Likewise, there was a significant increase in the latency to locate the platform in Morris water maze, time to traverse the balance beam and reduced hanging time on the wire test between the control and the PE treated. PE could lead to impaired neuronal signalling through demyelination which may contributes significantly to long-term sensorimotor and cognitive deficit.

摘要

子痫前期 (PE) 是一种妊娠并发症综合征,影响包括大脑在内的多个器官,在产后母亲和后代中仍然存在。我们通过发育评估 PE 大鼠模型大脑中的少突胶质细胞表达,以及 PE 样大鼠模型后代以后可能发生的认知变化和其他行为改变。通过给怀孕大鼠饮用 N-硝基-L-精氨酸甲酯 (L-NAME) 将其分为早发型和晚发型组,从妊娠第 8-17 天开始给药。在整个妊娠期间,大鼠可以自由饮水。在妊娠第 19 天、产后第 1 天和第 60 天,处死大鼠并取出大脑进行进一步分析。在产后第 60 天处死之前,对后代进行认知和感觉运动障碍的行为研究。结果表明,PE 在妊娠第 19 天大脑中的 OLIG2 表达显著下调,并持续到产后第 60 天。同样,在 Morris 水迷宫中寻找平台的潜伏期、平衡木穿越时间和金属丝悬挂时间都显著增加。PE 可能通过脱髓鞘导致神经元信号受损,这可能会导致长期的感觉运动和认知缺陷。

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