Neurotoxicity of Ammonia

Overview

Journal Neurochem Res

Specialties Chemistry
Neurology

Date 2016 Jul 29

PMID 27465396

Citations 31

Authors

Simo S Oja

Pirjo Saransaari

Esa R Korpi

Affiliations

Soon will be listed here.

Abstract

Abnormal liver function has dramatic effects on brain functions. Hyperammonemia interferes profoundly with brain metabolism, astrocyte volume regulation, and in particular mitochondrial functions. Gene expression in the brain and excitatory and inhibitory neurotransmission circuits are also affected. Experiments with a number of pertinent animal models have revealed several potential mechanisms which could underlie the pathological phenomena occurring in hepatic encephalopathy.

Citing Articles

Glutamine-glutamate centered metabolism as the potential therapeutic target against Japanese encephalitis virus-induced encephalitis.

Li M, Yuan H, Yang X, Lei Y, Lian J Cell Biosci. 2025; 15(1):6.

PMID: 39844330 PMC: 11755858. DOI: 10.1186/s13578-024-01340-3.

The Metabolic Impact of Nonalcoholic Fatty Liver Disease on Cognitive Dysfunction: A Comprehensive Clinical and Pathophysiological Review.

Giuffre M, Merli N, Pugliatti M, Moretti R Int J Mol Sci. 2024; 25(6).

PMID: 38542310 PMC: 10970252. DOI: 10.3390/ijms25063337.

Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD.

Mao Z, Gao Z, Ji T, Huan S, Yin G, Chen L Lipids Health Dis. 2024; 23(1):58.

PMID: 38395962 PMC: 10885469. DOI: 10.1186/s12944-024-02043-x.

A narrative review about cognitive impairment in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Another matter to face through a holistic approach.

Meroni M, Longo M, Paolini E, Dongiovanni P J Adv Res. 2024; 68:231-240.

PMID: 38369241 PMC: 11785580. DOI: 10.1016/j.jare.2024.02.007.

Metabolic alterations in the right anterior insula among patients with cirrhosis without overt hepatic encephalopathy: a magnetic resonance spectroscopy study.

Huang N, Huang H, Dong Q, Wen Y, Li D, Li J Front Neurol. 2024; 14:1291478.

PMID: 38283679 PMC: 10811796. DOI: 10.3389/fneur.2023.1291478.

References

Itzhak Y, DOMBRO R, Norenberg M . Acute liver failure and hyperammonemia increase peripheral-type benzodiazepine receptor binding and pregnenolone synthesis in mouse brain. Brain Res. 1995; 705(1-2):345-8. DOI: 10.1016/0006-8993(95)01244-3. View

Llansola M, Erceg S, Hernandez-Viadel M, Felipo V . Prevention of ammonia and glutamate neurotoxicity by carnitine: molecular mechanisms. Metab Brain Dis. 2003; 17(4):389-97. DOI: 10.1023/a:1021922305036. View

Gonzalez-Usano A, Cauli O, Agusti A, Felipo V . Hyperammonemia alters the modulation by different neurosteroids of the glutamate-nitric oxide-cyclic GMP pathway through NMDA- GABAA - or sigma receptors in cerebellum in vivo. J Neurochem. 2012; 125(1):133-43. DOI: 10.1111/jnc.12119. View

Norenberg M, Jayakumar A, Rama Rao K . Oxidative stress in the pathogenesis of hepatic encephalopathy. Metab Brain Dis. 2004; 19(3-4):313-29. DOI: 10.1023/b:mebr.0000043978.91675.79. View

Blei A . Brain edema in acute liver failure: can it be prevented? Can it be treated?. J Hepatol. 2007; 46(4):564-9. PMC: 3189486. DOI: 10.1016/j.jhep.2007.01.011. View

Leke R, Bak L, Anker M, Melo T, Sorensen M, Keiding S . Detoxification of ammonia in mouse cortical GABAergic cell cultures increases neuronal oxidative metabolism and reveals an emerging role for release of glucose-derived alanine. Neurotox Res. 2010; 19(3):496-510. DOI: 10.1007/s12640-010-9198-7. View

Pichili V, Rama Rao K, Jayakumar A, Norenberg M . Inhibition of glutamine transport into mitochondria protects astrocytes from ammonia toxicity. Glia. 2007; 55(8):801-9. DOI: 10.1002/glia.20499. View

Kruczek C, Gorg B, Keitel V, Bidmon H, Schliess F, Haussinger D . Ammonia increases nitric oxide, free Zn(2+), and metallothionein mRNA expression in cultured rat astrocytes. Biol Chem. 2011; 392(12):1155-65. DOI: 10.1515/BC.2011.199. View

Kosenko E, Kaminsky Y, Grau E, Minana M, Grisolia S, Felipo V . Nitroarginine, an inhibitor of nitric oxide synthetase, attenuates ammonia toxicity and ammonia-induced alterations in brain metabolism. Neurochem Res. 1995; 20(4):451-6. DOI: 10.1007/BF00973101. View

10.

Butterworth R . Altered glial-neuronal crosstalk: cornerstone in the pathogenesis of hepatic encephalopathy. Neurochem Int. 2010; 57(4):383-8. DOI: 10.1016/j.neuint.2010.03.012. View

11.

Zielinska M, Law R, Albrecht J . Excitotoxic mechanism of cell swelling in rat cerebral cortical slices treated acutely with ammonia. Neurochem Int. 2003; 43(4-5):299-303. DOI: 10.1016/s0197-0186(03)00015-9. View

12.

Albrecht J . Roles of neuroactive amino acids in ammonia neurotoxicity. J Neurosci Res. 1998; 51(2):133-8. DOI: 10.1002/(SICI)1097-4547(19980115)51:2<133::AID-JNR1>3.0.CO;2-E. View

13.

Matsuoka M, Igisu H . Comparison of the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia. Biochem Pharmacol. 1993; 46(1):159-64. DOI: 10.1016/0006-2952(93)90360-9. View

14.

Zorumski C, Paul S, Izumi Y, Covey D, Mennerick S . Neurosteroids, stress and depression: potential therapeutic opportunities. Neurosci Biobehav Rev. 2012; 37(1):109-22. PMC: 3591791. DOI: 10.1016/j.neubiorev.2012.10.005. View

15.

Norenberg M, Rama Rao K, Jayakumar A . Mechanisms of ammonia-induced astrocyte swelling. Metab Brain Dis. 2005; 20(4):303-18. DOI: 10.1007/s11011-005-7911-7. View

16.

Felipo V, Hermenegildo C, Montoliu C, LLansola M, Minana M . Neurotoxicity of ammonia and glutamate: molecular mechanisms and prevention. Neurotoxicology. 1998; 19(4-5):675-81. View

17.

Schousboe A, Waagepetersen H, Leke R, Bak L . Effects of hyperammonemia on brain energy metabolism: controversial findings in vivo and in vitro. Metab Brain Dis. 2014; 29(4):913-7. DOI: 10.1007/s11011-014-9513-8. View

18.

Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei A . Hepatic encephalopathy--definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002; 35(3):716-21. DOI: 10.1053/jhep.2002.31250. View

19.

Murthy C, Rama Rao K, Bai G, Norenberg M . Ammonia-induced production of free radicals in primary cultures of rat astrocytes. J Neurosci Res. 2001; 66(2):282-8. DOI: 10.1002/jnr.1222. View

20.

Anderzhanova E, Oja S, Saransaari P, Albrecht J . Changes in the striatal extracellular levels of dopamine and dihydroxyphenylacetic acid evoked by ammonia and N-methyl-D-aspartate: modulation by taurine. Brain Res. 2003; 977(2):290-3. DOI: 10.1016/s0006-8993(03)02777-x. View