西洛他唑抑制PDE3改善产前酒精诱导的实验性ADHD的行为和生化缺陷

Q4 Pharmacology, Toxicology and Pharmaceutics
Niti Sharma, B. Sharma, Neerupma Dhiman, L. Golani
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引用次数: 2

摘要

注意缺陷多动障碍(ADHD)是一种病因和表型复杂的神经发育障碍。众所周知,母亲饮酒会对后代产生有害影响,产生ADHD相关表型。磷酸二酯酶-3 (PDE3)已被证明对各种大脑状况有益。为了研究一种选择性PDE3抑制剂的作用,我们评估了西洛他唑给药对产前酒精暴露(PAE) ADHD模型核心表型的影响。通过在妊娠第8-20天将动物暴露于6/4 g.kg-1(工作日/周末)乙醇和西洛他唑(30/60 mg)来建立PAE。对暴露于酒精的雌性后代(PND21-48)给予kg-1 p.o.)。为了确定可能的机制,研究人员在额叶皮质、小脑和纹状体中研究了对神经元功能蛋白标志物的影响,如神经元存活- bdnf、神经元转录因子- pcreb、脑炎症(IL-6、IL-10和TNF-α)和脑氧化应激(TBARS和GSH)。此外,还评估了对多动症、注意力不集中和焦虑等行为的影响。PAE诱导实验动物过度运动、注意力不集中和焦虑。给PAE组动物西洛他唑可改善行为缺陷。西洛他唑导致PAE组不同脑区BDNF、pCREB、IL-10、GSH水平显著升高,TNF-α、IL-6、TBARS水平显著降低。西洛他唑是一种选择性PDE3抑制剂,可能通过改变与神经元存活、神经元转录因子、脑炎症和脑氧化应激相关的蛋白质标志物来纠正与ADHD相关的行为表型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
PDE3 Inhibition by Cilostazol Ameliorated Behavioral and Biochemical Deficits in Prenatal Alcohol Induced Experimental ADHD
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with complex aetiology and phenotypes. Maternal consumption of alcohol is known to produce deleterious effects in the progeny, generating ADHD related phenotypes. Phosphodiesterase-3 (PDE3) has been shown to provide benefits in various brain conditions. To investigate the role of a selective PDE3 inhibitor, effects of cilostazol administration on core phenotypes of prenatal alcohol exposure (PAE) model of ADHD were assessed. PAE was established by exposing animals to 6/4 g.kg-1 (weekdays/weekends) ethyl alcohol from gestational day 8-20 and cilostazol (30/60 mg.kg-1 p.o.) was administered to the offspring (PND21-48) of females exposed to ethyl alcohol. To identify probable mechanisms involved, the effects on protein markers of neuronal function such as, neuronal survival-BDNF, neuronal transcription factor-pCREB, brain inflammation (IL-6, IL-10 and TNF-α) and brain oxidative stress (TBARS and GSH) were studied in frontal cortex, cerebellum, and striatum. Also, effects on behaviour such as hyperactivity, inattention and anxiety were assessed. PAE induced hyper-locomotion, inattention, and anxiety in tested animals. Administration of cilostazol to PAE group of animals resulted in amelioration of behavioural deficits. Also, cilostazol resulted in a significant increase in the levels of BDNF, pCREB, IL-10 and GSH along with significant decrease in TNF-α, IL-6 and TBARS in different brain areas of PAE group. Cilostazol, a selective PDE3 inhibitor rectified behavioural phenotypes associated with ADHD, possibly by altering protein markers associated with neuronal survival, neuronal transcription factor, brain inflammation, and brain oxidative stress.
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来源期刊
Current Enzyme Inhibition
Current Enzyme Inhibition Pharmacology, Toxicology and Pharmaceutics-Drug Discovery
CiteScore
1.30
自引率
0.00%
发文量
30
期刊介绍: Current Enzyme Inhibition aims to publish all the latest and outstanding developments in enzyme inhibition studies with regards to the mechanisms of inhibitory processes of enzymes, recognition of active sites, and the discovery of agonists and antagonists, leading to the design and development of new drugs of significant therapeutic value. Each issue contains a series of timely, in-depth reviews written by leaders in the field, covering a range of enzymes that can be exploited for drug development. Current Enzyme Inhibition is an essential journal for every pharmaceutical and medicinal chemist who wishes to have up-to-date knowledge about each and every development in the study of enzyme inhibition.
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