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吗啡暴露对子代新物体记忆的影响:组蛋白 H3 和 ΔFosB 的作用。

Effect of morphine exposure on novel object memory of the offspring: The role of histone H3 and ΔFosB.

机构信息

Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran.

Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Brain Res Bull. 2020 Mar;156:141-149. doi: 10.1016/j.brainresbull.2020.01.011. Epub 2020 Jan 17.

Abstract

It has been demonstrated that alteration in histone acetylation in the regions of the brain involved in the reward which may have an important role in morphine addiction. It is well established that epigenetic changes prior to birth influence the function and development of the brain. The current study was designed to evaluate changes in novel object memory, histone acetylation and ΔFosB in the brain of the offspring of morphine-withdrawn parents. Male and female Wistar rats received morphine orally for 21 following days. After ten days of abstinent, they were prepared for mating. The male offspring of the first parturition were euthanized on postnatal days 5, 21, 30 and 60. The novel object recognition (NOR) test was performed on adult male offspring. The amount of acetylated histone H3 and ΔFosB were evaluated in the prefrontal cortex (PFC) and hippocampus using western blotting. Obtained results indicated that the discrimination index in the NOR test was decreased in the offspring of morphine-withdrawn parents as compared with morphine-naïve offspring. In addition, the level of acetylated histone H3 was decreased in the PFC and hippocampus in the offspring of morphine-withdrawn parents during lifetime (postnatal days 5, 21, 30 and 60). In the case of ΔFosB, it also decreased in these regions in the morphine-withdrawn offspring. These results demonstrated that parental morphine exposure affects NOR memory, and decreased the level of histone H3 acetylation and ΔFosB in the PFC and hippocampus. Taken together, the effect of morphine might be transmitted to the next generation even after stop consuming morphine.

摘要

已经证明,在涉及奖励的大脑区域中组蛋白乙酰化的改变可能在吗啡成瘾中起重要作用。 先前的研究已经证实,出生前的表观遗传变化会影响大脑的功能和发育。 本研究旨在评估吗啡戒断父母后代的新物体记忆、组蛋白乙酰化和ΔFosB 的变化。 雄性和雌性 Wistar 大鼠连续 21 天口服给予吗啡。 戒断 10 天后,它们准备交配。 第一胎分娩的雄性后代在产后第 5、21、30 和 60 天被安乐死。 对成年雄性后代进行新物体识别(NOR)测试。 使用 Western blot 法评估前额叶皮层(PFC)和海马中的乙酰化组蛋白 H3 和ΔFosB 的量。 结果表明,与吗啡未处理的后代相比,吗啡戒断父母的后代在 NOR 测试中的辨别指数降低。 此外,在一生中(产后第 5、21、30 和 60 天),吗啡戒断父母的后代的 PFC 和海马中的乙酰化组蛋白 H3 水平降低。 就 ΔFosB 而言,在吗啡戒断的后代中,这些区域的水平也降低了。 这些结果表明,父母的吗啡暴露会影响 NOR 记忆,并降低 PFC 和海马中组蛋白 H3 乙酰化和 ΔFosB 的水平。 综上所述,即使停止消耗吗啡,吗啡的作用也可能传递给下一代。

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