INTRACEREBROVENTRICULAR ADMINISTRATION OF L-ARGININE IMPROVES SPATIAL MEMORY ACQUISITION IN TRIPLE TRANSGENIC MICE VIA REDUCTION OF OXIDATIVE STRESS AND APOPTOSIS
INTRACEREBROVENTRICULAR ADMINISTRATION OF L-ARGININE IMPROVES SPATIAL MEMORY ACQUISITION IN TRIPLE TRANSGENIC MICE VIA REDUCTION OF OXIDATIVE STRESS AND APOPTOSIS
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DOI：
10.1515/tnsci-2018-0009
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发表时间：
2018-01-01
影响因子：
2.1
通讯作者：
Samson, Abraham O.
中科院分区：
文献类型：
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作者：
Fonar, Gennadiy;Polis, Baruh;Samson, Abraham O.
精氨酸是最通用的半必需氨基酸之一。除了在蛋白质生物合成中的主要作用外，精氨酸还参与尿素循环，并且是一氧化氮的前体。精氨酸缺乏与神经退行性疾病如帕金森病、亨廷顿病和阿尔茨海默病（AD）相关。在这项研究中，我们管理精氨酸脑室内的小鼠模型的AD和评估的认知功能，在一组行为测试。此外，精氨酸对突触可塑性的影响进行了测试，通过评估海马长时程增强（LTP）的电生理。精氨酸对β淀粉样变性的作用进行了免疫化学测试。在体外对PC-12细胞评价精氨酸在预防细胞毒性和细胞凋亡中的作用。结果表明，脑室内施用精氨酸改善了3xTg-AD小鼠的空间记忆获得，然而，没有显著减少神经元内β淀粉样变性。精氨酸对LTP的影响很小或没有影响，并且不能挽救A β诱导的LTP恶化。然而，精氨酸具有神经保护和抗凋亡特性。
Arginine is one of the most versatile semi-essential amino acids. Further to the primary role in protein biosynthesis, arginine is involved in the urea cycle, and it is a precursor of nitric oxide. Arginine deficiency is associated with neurodegenerative diseases such as Parkinson's, Huntington's and Alzheimer's diseases (AD). In this study, we administer arginine intracerebroventricularly in a murine model of AD and evaluate cognitive functions in a set of behavioral tests. In addition, the effect of arginine on synaptic plasticity was tested electrophysiologically by assessment of the hippocampal long-term potentiation (LTP). The effect of arginine on beta amyloidosis was tested immunohistochemically. A role of arginine in the prevention of cytotoxicity and apoptosis was evaluated in vitro on PC-12 cells. The results indicate that intracerebroventricular administration of arginine improves spatial memory acquisition in 3xTg-AD mice, however, without significantly reducing intraneuronal beta amyloidosis. Arginine shows little or no impact on LTP and does not rescue LTP deterioration induced by A beta. Nevertheless, arginine possesses neuroprotective and antiapoptotic properties.