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Apelin-13 attenuates spatial memory impairment by anti-oxidative, anti-apoptosis, and anti-inflammatory mechanism against ethanol neurotoxicity in the neonatal rat hippocampus
Neuropeptides ( IF 2.9 ) Pub Date : 2021-02-18 , DOI: 10.1016/j.npep.2021.102130
Fahimeh Mohseni 1 , Behzad Garmabi 2 , Mehdi Khaksari 3
Affiliation  

It has been shown that alcohol consumption by pregnant women can have detrimental effects on the developing fetus and lead to fetal alcohol spectrum disorders (FASD). Exposure to alcohol in rat pups during this period causes long-term changes in the structure of the animal's hippocampus, leading to impaired hippocampal-related brain functions such as navigation tasks and spatial memory. Apelin-13, a principal neuropeptide with inhibitory effects on neuroinflammation and brain oxidative stress production, has beneficial properties on memory impairment and neuronal injury. The protective effects of apelin-13 have been evaluated on ethanol-related neurotoxicity in the hippocampus of rat pups. Rat pups from 2 until 10 postnatal day, similar to the third trimester of pregnancy in humans, were intubated total daily dose of ethanol (5/27 g/kg/day). Immediately after intubation, 25 and 50 μg/ kg of apelin-13 was injected subcutaneously. By using Morris water maze task, the hippocampus- dependent memory and spatial learning were evaluated 36 days after birth. Then, Immunohistochemical staining was done to determine the levels of GFAP and caspase-3. ELISA assay was also performed to measure both TNF-α and antioxidant enzymes levels. The current study demonstrates that administration of apelin-13 attenuates spatial memory impairment significantly (P < 0.001). After ethanol neurotoxicity, apelin-13 could also increase the catalase level (P < 0.001), activity of total superoxide dismutase as well as glutathione concentration noticeably (P < 0.05). Other impacts of it could be mentioned as attenuating TNF-α production and also preventing lipid peroxidation (P < 0.001). In addition, the results showed that the level of GFAP as a neuroinflammation factor and the number of active caspase-3 positive cells can be decreased by apelin-13 (P < 0.01). Regarding the protective effects of apelin-13 against ethanol-induced neurotoxicity, it is a promising therapeutic choice for FASD; but more studies are needed.



中文翻译:

Apelin-13通过抗氧化、抗凋亡和抗炎机制减轻新生大鼠海马乙醇神经毒性的空间记忆障碍

研究表明,孕妇饮酒会对发育中的胎儿产生不利影响,并导致胎儿酒精谱系障碍 (FASD)。在此期间幼鼠接触酒精会导致动物海马结构的长期变化,导致与海马相关的大脑功能受损,例如导航任务和空间记忆。Apelin-13 是一种主要的神经肽,对神经炎症和脑氧化应激产生具有抑制作用,对记忆障碍和神经元损伤具有有益的特性。已经评估了 apelin-13 对幼鼠海马中乙醇相关神经毒性的保护作用。从出生后第 2 天到第 10 天,类似于人类怀孕的第三个三个月,给幼鼠插管每日总剂量的乙醇(5/27 g/kg/天)。插管后立即皮下注射25和50μg/kg的apelin-13。通过使用莫里斯水迷宫任务,在出生后 36 天评估海马依赖性记忆和空间学习。然后,进行免疫组织化学染色以确定 GFAP 和 caspase-3 的水平。还进行了 ELISA 测定以测量 TNF-α 和抗氧化酶水平。目前的研究表明,apelin-13 的给药显着减轻了空间记忆障碍。还进行了 ELISA 测定以测量 TNF-α 和抗氧化酶水平。目前的研究表明,apelin-13 的给药显着减轻了空间记忆障碍。还进行了 ELISA 测定以测量 TNF-α 和抗氧化酶水平。目前的研究表明,apelin-13 的给药显着减轻了空间记忆障碍。P  < 0.001)。乙醇神经毒性后,apelin-13还可显着提高过氧化氢酶水平(P < 0.001)、总超氧化物歧化酶活性和谷胱甘肽浓度(P  < 0.05)。它的其他影响可以被提及为减弱 TNF-α 的产生并防止脂质过氧化(P  < 0.001)。此外,结果显示apelin-13可降低GFAP作为神经炎症因子的水平和活性caspase-3阳性细胞的数量(P  < 0.01)。关于apelin-13对乙醇诱导的神经毒性的保护作用,它是FASD的一个有希望的治疗选择;但还需要更多的研究。

更新日期:2021-02-25
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