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Journal of Education, Health and Sport

Glutamine synthetase expression in the brain during experimental acute liver failure (immunohistochemical study)
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Glutamine synthetase expression in the brain during experimental acute liver failure (immunohistochemical study)

Authors

  • T. Shulyatnikova Zaporizhzhia State Medical University
  • V. Tumanskiy Zaporizhzhia State Medical University

DOI:

https://doi.org/10.12775/JEHS.2021.11.10.033

Keywords

acute hepatic encephalopathy, astroglial reactivity, GS

Abstract

The aim of the study was to determine the immunohistochemical level of glutamine synthetase (GS) expression in different brain regions in the conditions of experimental acute liver failure in rats.

Materials and methods. The study was conducted in Wistar rats: 5 sham (control) animals and 10 rats with acetaminophen induced liver failure model (AILF). The immunohistochemical study of GS expression in the sensorimotor cortex, white matter, hippocampus, thalamus, caudate nucleus/putamen was carried out in the period of 12-24 h after acetaminophen treatment.

Results. Beginning from the 6th hour after acetaminophen treatment all AILF-animals showed the progressive increase in clinical signs of acute brain disfunction finished in 6 rats by comatose state up to 24 h - they constituted subgroup AILF-B, “non-survived”. 4 animals survived until the 24 h - subgroup AILF-A, “survived”. In the AILF-B group, starting from 16 to 24 hours after treatment, a significant (relative to control) regionally-specific dynamic increase in the level of GS expression was observed in the brain: in the cortex – by 307.33 %, in the thalamus – by 249.47%, in the hippocampus – by 245.53%, in the subcortical white matter – by 126.08%, from 12th hour – in the caudate nucleus/putamen, by 191.66 %; with the most substantive elevation of GS expression in the cortex: by 4.07 times.

Conclusion. Starting from the 16th hours after the acetaminophen treatment (from the 12th h in the caudate nucleus/putamen region) and up to 24 h, it is observed reliable compared to control dynamic increase in GS protein expression in the cortex, white matter, hippocampus, thalamus, caudate nucleus/putamen of the rat brain with the most significant elevation in the cortex among other regions. The heterogeneity in the degree of GS expression rising in different brain regions potentially may indicate regions more permeable for ammonia and/or other systemic toxic factors as well as heterogeneous sensitivity of brain regions to deleterious agents in conditions of AILF. Subsequently, revealed diversity in the GS expression reflects the specificity of reactive response of local astroglia in the condition of AILF-encephalopathy during specific time-period. The dynamic increase in the GS expression associated with impairment of animal state, indicates involvement of increased GS levels in the mechanisms of experimental acute hepatic encephalopathy.

References

Hirode, G., Vittinghoff, E., & Wong, R. J. (2019). Increasing Burden of Hepatic Encephalopathy Among Hospitalized Adults: An Analysis of the 2010-2014 National Inpatient Sample. Digestive diseases and sciences, 64(6), 1448–1457. https://doi.org/10.1007/s10620-019-05576-9

Vilstrup, H., Amodio, P., Bajaj, J., Cordoba, J., Ferenci, P., Mullen, K. D., Weissenborn, K., & Wong, P. (2014). Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology (Baltimore, Md.), 60(2), 715–735. https://doi.org/10.1002/hep.27210

Amodio, P., & Montagnese, S. (2021). Lights and Shadows in Hepatic Encephalopathy Diagnosis. Journal of clinical medicine, 10(2), 341. https://doi.org/10.3390/jcm10020341

Weissenborn K. (2019). Hepatic Encephalopathy: Definition, Clinical Grading and Diagnostic Principles. Drugs, 79(Suppl 1), 5–9. https://doi.org/10.1007/s40265-018-1018-z

Ferenci P. (2017). Hepatic encephalopathy. Gastroenterology report, 5(2), 138–147. https://doi.org/10.1093/gastro/gox013

Jayakumar, A. R., & Norenberg, M. D. (2018). Hyperammonemia in Hepatic Encephalopathy. Journal of clinical and experimental hepatology, 8(3), 272–280. https://doi.org/10.1016/j.jceh.2018.06.007

Shulyatnikova T. & Shavrin V. (2017). Modern view on hepatic encephalopathy: basic terms and concepts of pathogenesis. Pathologia, 14(3), 371-380 (41). https://doi.org/10.14739/2310-1237.2017.3.118773

Brusilow, S. W., Koehler, R. C., Traystman, R. J., & Cooper, A. J. (2010). Astrocyte glutamine synthetase: importance in hyperammonemic syndromes and potential target for therapy. Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics, 7(4), 452–470. https://doi.org/10.1016/j.nurt.2010.05.015

Dasarathy, S., Mookerjee, R. P., Rackayova, V., Rangroo Thrane, V., Vairappan, B., Ott, P., & Rose, C. F. (2017). Ammonia toxicity: from head to toe? Metabolic brain disease, 32(2), 529–538. https://doi.org/10.1007/s11011-016-9938-3

Ochoa-Sanchez, R., Tamnanloo, F., & Rose, C. F. (2021). Hepatic Encephalopathy: From Metabolic to Neurodegenerative. Neurochemical research, 46(10), 2612–2625. https://doi.org/10.1007/s11064-021-03372-4

Liotta, E. M., & Kimberly, W. T. (2020). Cerebral edema and liver disease: Classic perspectives and contemporary hypotheses on mechanism. Neuroscience letters, 721, 134818. https://doi.org/10.1016/j.neulet.2020.134818

Walls, A. B., Waagepetersen, H. S., Bak, L. K., Schousboe, A., & Sonnewald, U. (2015). The glutamine-glutamate/GABA cycle: function, regional differences in glutamate and GABA production and effects of interference with GABA metabolism. Neurochemical research, 40(2), 402–409. https://doi.org/10.1007/s11064-014-1473-1

Zhou, Y., Eid, T., Hassel, B., & Danbolt, N. C. (2020). Novel aspects of glutamine synthetase in ammonia homeostasis. Neurochemistry international, 140, 104809. https://doi.org/10.1016/j.neuint.2020.104809

Jaeger, V., DeMorrow, S., & McMillin, M. (2019). The Direct Contribution of Astrocytes and Microglia to the Pathogenesis of Hepatic Encephalopathy. Journal of clinical and translational hepatology, 7(4), 352–361. https://doi.org/10.14218/JCTH.2019.00025

Batiuk, M. Y., Martirosyan, A., Wahis, J., de Vin, F., Marneffe, C., Kusserow, C., Koeppen, J., Viana, J. F., Oliveira, J. F., Voet, T., Ponting, C. P., Belgard, T. G., & Holt, M. G. (2020). Identification of region-specific astrocyte subtypes at single cell resolution. Nature communications, 11(1), 1220. https://doi.org/10.1038/s41467-019-14198-8

McGill, M. R., Williams, C. D., Xie, Y., Ramachandran, A., & Jaeschke, H. (2012). Acetaminophen-induced liver injury in rats and mice: comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity. Toxicology and applied pharmacology, 264(3), 387–394. https://doi.org/10.1016/j.taap.2012.08.015

Mossanen, J. C., & Tacke, F. (2015). Acetaminophen-induced acute liver injury in mice. Laboratory animals, 49(1 Suppl), 30–36. https://doi.org/10.1177/0023677215570992

Shulyatnikova T, Shavrin V. (2021). Mobilisation and redistribution of multivesicular bodies to the endfeet of reactive astrocytes in acute endogenous toxic encephalopathies. Brain Research, 1751:147174. https://doi.org/10.1016/j.brainres.2020.147174.

Mitchell, R. A., Rathi, S., Dahiya, M., Zhu, J., Hussaini, T., & Yoshida, E. M. (2020). Public awareness of acetaminophen and risks of drug induced liver injury: Results of a large outpatient clinic survey. PloS one, 15(3), e0229070. https://doi.org/10.1371/journal.pone.0229070

Butterworth R. F. (2015). Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure. Journal of clinical and experimental hepatology, 5(Suppl 1), S96–S103. https://doi.org/10.1016/j.jceh.2014.02.004

Häussinger, D., Görg, B., Reinehr, R., & Schliess, F. (2005). Protein tyrosine nitration in hyperammonemia and hepatic encephalopathy. Metabolic brain disease, 20(4), 285–294. https://doi.org/10.1007/s11011-005-7908-2

Aldridge, D. R., Tranah, E. J., & Shawcross, D. L. (2015). Pathogenesis of hepatic encephalopathy: role of ammonia and systemic inflammation. Journal of clinical and experimental hepatology, 5(Suppl 1), S7–S20. https://doi.org/10.1016/j.jceh.2014.06.004

Hakvoort, T. B., He, Y., Kulik, W., Vermeulen, J. L., Duijst, S., Ruijter, J. M., Runge, J. H., Deutz, N. E., Koehler, S. E., & Lamers, W. H. (2017). Pivotal role of glutamine synthetase in ammonia detoxification. Hepatology (Baltimore, Md.), 65(1), 281–293. https://doi.org/10.1002/hep.28852

He, Y., Hakvoort, T. B., Vermeulen, J. L., Labruyère, W. T., De Waart, D. R., Van Der Hel, W. S., Ruijter, J. M., Uylings, H. B., & Lamers, W. H. (2010). Glutamine synthetase deficiency in murine astrocytes results in neonatal death. Glia, 58(6), 741–754. https://doi.org/10.1002/glia.20960

Zhou, Y., Dhaher, R., Parent, M., Hu, Q. X., Hassel, B., Yee, S. P., Hyder, F., Gruenbaum, S. E., Eid, T., & Danbolt, N. C. (2019). Selective deletion of glutamine synthetase in the mouse cerebral cortex induces glial dysfunction and vascular impairment that precede epilepsy and neurodegeneration. Neurochemistry international, 123, 22–33. https://doi.org/10.1016/j.neuint.2018.07.009

Spodenkiewicz, M., Diez-Fernandez, C., Rüfenacht, V., Gemperle-Britschgi, C., & Häberle, J. (2016). Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis. Biology, 5(4), 40. https://doi.org/10.3390/biology5040040

Sandhu, M., Gruenbaum, B. F., Gruenbaum, S. E., Dhaher, R., Deshpande, K., Funaro, M. C., Lee, T. W., Zaveri, H. P., & Eid, T. (2021). Astroglial Glutamine Synthetase and the Pathogenesis of Mesial Temporal Lobe Epilepsy. Frontiers in neurology, 12, 665334. https://doi.org/10.3389/fneur.2021.665334

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Published

2021-10-29

How to Cite

1.
SHULYATNIKOVA, T. & TUMANSKIY, V. Glutamine synthetase expression in the brain during experimental acute liver failure (immunohistochemical study). Journal of Education, Health and Sport [online]. 29 October 2021, T. 11, nr 10, s. 342–356. [accessed 27.3.2023]. DOI 10.12775/JEHS.2021.11.10.033.
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Vol. 11 No. 10 (2021)

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Copyright (c) 2021 T. Shulyatnikova, V. Tumanskiy

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