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Agmatine improves the behavioral and cognitive impairments associated with chronic gestational ethanol exposure in rats
Brain Research Bulletin ( IF 3.5 ) Pub Date : 2020-11-23 , DOI: 10.1016/j.brainresbull.2020.11.015
Manish M Aglawe 1 , Mayur B Kale 1 , Sandip R Rahangdale 1 , Nandkishor R Kotagale 2 , Milind J Umekar 1 , Brijesh G Taksande 1
Affiliation  

Chronic maternal ethanol exposure leads to poor intelligence, impaired cognition and array of neurological symptoms in offsprings and commonly referred as fetal alcohol spectrum disorder (FASD). Despite high prevalence and severity, the neurochemical basis of FASD remains largely unexplored. The present study evaluated the pharmacological effects of agmatine in cognitive deficits associated with FAS in rat’s offsprings prenatally exposed to alcohol. Pregnant rats received ethanol in liquid modified diet during the entire gestational period of 21 days. Offsprings were treated with agmatine (20–80 mg/Kg, i.p.) during early postnatal days (PND: 21–35) and subsequently evaluated for anxiety in elevated plus maze (EPM), depression in forced swim test (FST) and learning and memory in Morris’s water maze (MWM) during post adolescent phase. Hippocampal agmatine, BDNF, TNF-α and IL-6 levels were also analyzed in prenatally ethanol exposed pups. Offsprings prenatally exposed to ethanol demonstrated delayed righting reflex, reduced exploratory behavior along with anxiety, depression-like behavior and impaired memory. These behavioral abnormalities were correlated with a significant reduction in hippocampal agmatine and BDNF levels and elevation in TNF-α and IL-6 immunocontent. Chronic agmatine (40 and 80 mg/Kg, i.p.) administration for 15 days (PND: 21–35), improved entries and time spent in open arm of EPM, decreased immobility time in FST. It also reduced latency to reach the platform location; increased the number of entries, time spent in platform quadrant and also number of crossing over platform quadrant when subjected to MWM test in prenatally ethanol exposed offsprings. This study provides functional evidences for the therapeutic potential of agmatine in cognitive impairment and other neurological complications associated with FASD.



中文翻译:

丁改善与大鼠慢性妊娠乙醇暴露相关的行为和认知障碍

母体长期接触乙醇会导致后代智力低下、认知受损和一系列神经系统症状,通常称为胎儿酒精谱系障碍 (FASD)。尽管患病率和严重程度很高,但 FASD 的神经化学基础在很大程度上仍未得到探索。本研究评估了胍丁胺对产前暴露于酒精的大鼠后代与 FAS 相关的认知缺陷的药理作用。在 21 天的整个妊娠期期间,怀孕的大鼠接受液体改良饮食中的乙醇。在出生后早期(PND:21-35)用胍丁胺(20-80 毫克/公斤,腹腔注射)治疗后代,随后评估高架十字迷宫 (EPM) 中的焦虑、强迫游泳测试 (FST) 中的抑郁以及学习和青春期后莫里斯水迷宫(MWM)中的记忆。还在产前乙醇暴露的幼崽中分析了海马胍丁胺、BDNF、TNF-α 和 IL-6 水平。出生前暴露于乙醇的后代表现出延迟的翻正反射、减少的探索行为以及焦虑、抑郁样行为和记忆力受损。这些行为异常与海马胍丁胺和 BDNF 水平的显着降低以及 TNF-α 和 IL-6 免疫含量的升高有关。慢性胍丁胺(40 和 80 毫克/公斤,腹腔注射)给药 15 天(PND:21-35),改善 EPM 开放臂的进入和时间,减少 FST 的不动时间。它还减少了到达平台位置的延迟;在出生前乙醇暴露的后代中进行 MWM 测试时,增加了条目数量、在平台象限中花费的时间以及跨越平台象限的数量。

更新日期:2020-12-13
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