Aminooxyacetic acid improves learning and memory in a rat model of chronic alcoholism.
Aminooxyacetic acid improves learning and memory in a rat model of chronic alcoholism.
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氨基氧乙酸可改善慢性酒精中毒大鼠模型的学习和记忆
DOI：
10.4103/1673-5374.237120
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发表时间：
2018-09
影响因子：
6.1
通讯作者：
Xu YM
中科院分区：
文献类型：
--
作者：
Du AL;Qin HZ;Jiang HB;Fu PY;Lou K;Xu YM
慢性酒精中毒严重损害中枢神经系统，导致学习和记忆受损。慢性酒精中毒的细胞损伤与硫化氢(H2S)水平升高和钙离子超载密切相关。氨基氧乙酸是一种胱硫醚-β-合成酶活性抑制剂，可以减少大脑中硫化氢的形成。本研究旨在观察氨基氧乙酸对慢性酒精中毒大鼠学习记忆的影响。将大鼠随机分为3组。对照组大鼠饮用纯净水28d。模型组大鼠灌胃6%酒精28d建立酒精中毒大鼠模型。氨基氧乙酸组同时灌胃6%酒精28d，第15~28d每日腹腔注射氨基氧乙酸5 mg/kg。用Morris水迷宫测试学习记忆能力。用电子显微镜观察海马区线粒体的超微结构。用分光光度法间接测定海马区H_2S水平，用商用试剂盒测定ATPase活性。免疫组织化学和免疫印迹法检测髓鞘碱性蛋白的表达。与对照组比较，模型组大鼠第2、3、4天航行试验潜伏期延长，游泳距离延长。在第5天的空间探索试验中，模型组大鼠跨越平台的次数减少。与对照组相比，模型组大鼠海马区出现线粒体脊裂、肿胀或变形，海马区H_2S水平升高，线粒体ATPase活性降低，髓鞘碱性蛋白表达下调。氨基氧乙酸组较模型组上述各项指标均有改善。提示氨基氧乙酸可改善慢性酒精中毒模型大鼠的学习记忆能力，其机制可能与降低海马区H_2S水平和线粒体ATPase活性，上调海马髓鞘碱性蛋白水平有关。
Chronic alcoholism seriously damages the central nervous system and leads to impaired learning and memory. Cell damage in chronic alcoholism is strongly associated with elevated levels of hydrogen sulfide (H2S) and calcium ion overload. Aminooxyacetic acid is a cystathionine-β-synthase activity inhibitor that can reduce H2S formation in the brain. This study sought to observe the effect of aminooxyacetic acid on learning and memory in a chronic alcoholism rat model. Rats were randomly divided into three groups. Rats in the control group were given pure water for 28 days. Rats in the model group were given 6% alcohol for 28 days to establish an alcoholism rat model. Rats in the aminooxyacetic acid remedy group were also given 6% alcohol for 28 days and were also intraperitoneally injected daily with aminooxyacetic acid (5 mg/kg) from day 15 to day 28. Learning and memory was tested using the Morris water maze test. The ultrastructure of mitochondria in the hippocampus was observed by electron microscopy. H2S levels in the hippocampus were measured indirectly by spectrophotometry, and ATPase activity was measured using a commercial kit. The expression of myelin basic protein was determined by immunohistochemistry and western blotting. Compared with the control group, latency and swimming distance were prolonged in the navigation test on days 2, 3, and 4 in the model group. In the spatial probe test on day 5, the number of platform crosses was reduced in the model group. Cristae cracks, swelling or deformation of mitochondria appeared in the hippocampus, the hippocampal H2S level was increased, the mitochondrial ATPase activity was decreased, and the expression of myelin basic protein in the hippocampus was down-regulated in the model group compared with the control group. All the above indexes were ameliorated in the aminooxyacetic acid remedy group compared with the model group. These findings indicate that aminooxyacetic acid can improve learning and memory in a chronic alcoholism rat model, which may be associated with reduction of hippocampal H2S level and mitochondrial ATPase activity, and up-regulation of myelin basic protein levels in the hippocampus.
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DOI：
10.1111/acer.13431
发表时间：
2017-08
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Le Berre AP;Fama R;Sullivan EV
通讯作者：
Sullivan EV
DOI：
10.1111/j.1530-0277.2011.01722.x
发表时间：
2012-07
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Nam HW;McIver SR;Hinton DJ;Thakkar MM;Sari Y;Parkinson FE;Haydon PG;Choi DS
通讯作者：
Choi DS
影响因子：
4
作者：
Donovan, J.;Wong, P. S.;Ralevic, V.
通讯作者：
Ralevic, V.
DOI：
10.1016/j.bbabio.2015.09.013
发表时间：
2016-01
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
King MS;Kerr M;Crichton PG;Springett R;Kunji ERS
通讯作者：
Kunji ERS
影响因子：
2.9
作者：
Mooney, SM;Miller, MW
通讯作者：
Miller, MW