Inborn Errors of Metabolism, Clinical Chemistry Laboratory, Center Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Mol Genet Metab. 2010;100 Suppl 1:S53-8. doi: 10.1016/j.ymgme.2010.02.011. Epub 2010 Feb 14.
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.
高氨血症可导致发育中大脑的不可逆转损伤，形成皮质萎缩、脑室扩大、脱髓鞘或灰白质密度降低。在涉及的各种致病机制中，脑能量的改变已得到证实。特别是，我们可以表明，氨暴露通过改变允许肌酸合成（AGAT 和 GAMT）和转运（SLC6A8）的基因在脑细胞中产生肌酸的继发性缺乏。另一方面，已知肌酸给药可以在各种神经退行性过程中发挥保护作用。我们还可以表明，在氨暴露下进行肌酸共同处理可以保护发育中的脑细胞免受氨的一些有害影响，特别是轴突生长受损。本文重点介绍氨暴露对发育中脑细胞肌酸代谢和转运的影响，以及在暴露于铵的大脑中肌酸的潜在神经保护特性。
