Ammonia toxicity to the brain: Effects on creatine metabolism and transport and protective roles of creatine
Ammonia toxicity to the brain: Effects on creatine metabolism and transport and protective roles of creatine
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DOI：
10.1016/j.ymgme.2010.02.011
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发表时间：
2010-01-01
影响因子：
3.8
通讯作者：
Braissant, Olivier
中科院分区：
文献类型：
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作者：
Braissant, Olivier
高氨血症会对发育中的大脑造成不可逆的损害，形成皮质萎缩、脑室扩大、脱髓鞘或灰白质低密度。在所涉及的各种致病机制中，脑能量的改变已被证实。特别是，我们可以证明，通过改变允许肌酸合成（AGAT 和 GAMT）和运输（SLC6A8）的基因的大脑表达和活性，氨暴露会导致脑细胞中肌酸的继发性缺乏。另一方面，众所周知，肌酸给药可以在各种神经退行性过程中发挥保护作用。我们还可以证明，在氨暴露下肌酸联合治疗可以保护发育中的脑细胞免受氨的一些有害影响，特别是轴突生长障碍。本文重点关注氨暴露对发育中的脑细胞中肌酸代谢和运输的影响，以及肌酸在暴露于铵的大脑中的潜在神经保护特性。 (C) 2010 Elsevier Inc. 保留所有权利。
Hyperammonemia can provoke irreversible damage to the developing brain, with the formation of cortical atrophy, ventricular enlargement, demyelination or gray and white matter hypodensities. Among the various pathogenic mechanisms involved, alterations in cerebral energy have been demonstrated. In particular, we could show that ammonia exposure generates a secondary deficiency in creatine in brain cells, by altering the brain expression and activity of the genes allowing creatine synthesis (AGAT and GAMT) and transport (SLC6A8). On the other hand, it is known that creatine administration can exert protective effects in various neurodegenerative processes. We could also show that creatine co-treatment under ammonia exposure can protect developing brain cells from some of the deleterious effects of ammonia, in particular axonal growth impairment. This article focuses on the effects of ammonia exposure on creatine metabolism and transport in developing brain cells, and on the potential neuroprotective properties of creatine in the brain exposed to ammonium. (C) 2010 Elsevier Inc. All rights reserved.