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Reassessing the role of astrocytes in ammonia neurotoxicity

Nature Medicine volume 19, pages 1572–1574 (2013)Cite this article

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High blood ammonia, as seen in severe liver disease and urea cycle disorders, is neurotoxic and difficult to treat. A new study shows that the toxic effects are caused by impaired astrocyte potassium buffering—not astrocyte swelling, as previously thought—and can be partially blocked by the diuretic bumetanide (pages 1643–1648).

Ammonia, a structurally simple yet biologically potent molecule, is extensively present in nature and crucially involved in a variety of processes ranging from industrial production of fertilizers to pH regulation and metabolism of nitrogen-containing compounds in living organisms. In the human body, as much as 4 g of ammonia is formed every day, mainly from the physiological action of bacterial enzymes on colonic content and from hydrolysis of glutamine in the cells of the small and large intestine by the enzyme glutaminase. A smaller amount of ammonia is also synthesized in other organs via one of several biochemical routes involving enzymes such as glutaminase, glutamic acid dehydrogenase and adenosine deaminase.

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Figure 1: Uptake, metabolism and proposed toxic mechanism of ammonia in the CNS.

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Authors and Affiliations

  1. Tore Eid is at the Departments of Laboratory Medicine and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA.,

    Tore Eid

  2. Tih-Shih W. Lee is at the Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.,

    Tih-Shih W Lee

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  1. Tore Eid
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  2. Tih-Shih W Lee
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Correspondence to Tore Eid.

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Eid, T., Lee, TS. Reassessing the role of astrocytes in ammonia neurotoxicity. Nat Med 19, 1572–1574 (2013). https://doi.org/10.1038/nm.3420

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