Koyuncuoglu Turkan, Turkyilmaz Mesut, Goren Bulent, Cetinkaya Merih, Cansev Mehmet, Alkan Tulin
Uludag University Medical School Department of Physiology, Bursa, Turkey.
Uludag University Medical School Department of Pharmacology, Bursa, Turkey.
Restor Neurol Neurosci. 2015;33(5):777-84. doi: 10.3233/RNN-150549.
A significant cause of neurological disability in newborns is hypoxic-ischemic encephalopathy (HIE), a disorder which involves an enhancement in histone deacetylase (HDAC) activity among underlying pathological mechanisms. We showed recently that exogenous administration of uridine to newborn rats with HIE reduced brain injury in a dose-dependent manner. The present study was performed to investigate whether uridine modulates histone acetylation/deacetylation balance in a neonatal rat model of HIE.
Newborn rats that were subjected to hypoxic-ischemic (HI) insult on postnatal day 7 (P7) were injected intraperitoneally with either saline or uridine (500 mg/kg) for three consecutive days. One day after completion of treatment, brains of pups were collected for evaluation of brain infarct volume, apoptosis, HDAC activity and acetylated-Histone H3 (Ac-H3) and H4 (Ac-H4) protein levels.
Results revealed that uridine administration reduced infarct volume, active Caspase-3 levels and HDAC activity while increasing the expressions of Ac-H3 and Ac-H4 proteins.
We conclude that one mechanism by which uridine provides neuroprotection in neonatal rat HIE model involves reduction in HDAC activity.
新生儿神经功能障碍的一个重要原因是缺氧缺血性脑病（HIE），该疾病在潜在病理机制中涉及组蛋白脱乙酰酶（HDAC）活性增强。我们最近发现，给患有HIE的新生大鼠外源性给予尿苷可剂量依赖性地减轻脑损伤。本研究旨在探讨尿苷是否能调节HIE新生大鼠模型中的组蛋白乙酰化/去乙酰化平衡。
在出生后第7天（P7）对新生大鼠进行缺氧缺血（HI）损伤，连续三天腹腔注射生理盐水或尿苷（500mg/kg）。治疗结束后一天，收集幼崽的大脑，评估脑梗死体积、细胞凋亡、HDAC活性以及乙酰化组蛋白H3（Ac-H3）和H4（Ac-H4）蛋白水平。
结果显示，给予尿苷可减少梗死体积、活性半胱天冬酶-3水平和HDAC活性，同时增加Ac-H3和Ac-H4蛋白的表达。
我们得出结论，尿苷在新生大鼠HIE模型中提供神经保护的一种机制涉及降低HDAC活性。
