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Antioxidants Reverse the Changes in the Cholinergic System Caused by L-Tyrosine Administration in Rats

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Abstract

Tyrosinemia type II is an inborn error of metabolism caused by a deficiency in the activity of the enzyme tyrosine aminotransferase, leading to tyrosine accumulation in the body. Although the mechanisms involved are still poorly understood, several studies have showed that higher levels of tyrosine are related to oxidative stress and therefore may affect the cholinergic system. Thus, the aim of this study was to investigate the effects of chronic administration of L-tyrosine on choline acetyltransferase activity (ChAT) and acetylcholinesterase (AChE) in the brain of rats. Moreover, we also examined the effects of one antioxidant treatment (N-acetylcysteine (NAC) + deferoxamine (DFX)) on cholinergic system. Our results showed that the chronic administration of L-tyrosine decreases the ChAT activity in the cerebral cortex, while the AChE activity was increased in the hippocampus, striatum, and cerebral cortex. Moreover, we found that the antioxidant treatment was able to prevent the decrease in the ChAT activity in the cerebral cortex. However, the increase in AChE activity induced by L-tyrosine was partially prevented the in the hippocampus and striatum, but not in the cerebral cortex. Our results also showed no differences in the aversive and spatial memory after chronic administration of L-tyrosine. In conclusion, the results of this study demonstrated an increase in AChE activity in the hippocampus, striatum, and cerebral cortex and an increase of ChAT in the cerebral cortex, without cognitive impairment. Furthermore, the alterations in the cholinergic system were partially prevented by the co-administration of NAC and DFX. Thus, the restored central cholinergic system by antioxidant treatment further supports the view that oxidative stress may be involved in the pathophysiology of tyrosinemia type II.

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Funding

This research was supported by grants from Programa de Pós-graduação em Ciências da Saúde – Universidade do Extremo Sul Catarinense (UNESC) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

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Authors and Affiliations

  1. Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, Criciúma, SC, 88806-000, Brazil

    Lara M. Gomes, Giselli Scaini, Milena Carvalho-Silva & Emilio L. Streck

  2. Laboratório de Erros Inatos do Metabolismo, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil

    Maria L. Gomes, Fernanda Malgarin & Patrícia F. Schuck

  3. Laboratório de Biologia Genômica e Molecular, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Luiza W. Kist & Maurício R. Bogo

  4. Laboratório de Sinalização Neural e Psicofarmacologia, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil

    Eduardo Pacheco Rico

  5. Laboratório de Neurociências, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil

    Alexandra I. Zugno, Pedro F. P. Deroza, Gislaine Z. Réus, Airam B. de Moura & João Quevedo

  6. Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    João Quevedo

  7. Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Gustavo C. Ferreira

Authors
  1. Lara M. Gomes
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  2. Giselli Scaini
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  3. Milena Carvalho-Silva
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  4. Maria L. Gomes
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  5. Fernanda Malgarin
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  6. Luiza W. Kist
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  7. Maurício R. Bogo
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  8. Eduardo Pacheco Rico
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  9. Alexandra I. Zugno
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  10. Pedro F. P. Deroza
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  11. Gislaine Z. Réus
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  12. Airam B. de Moura
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  13. João Quevedo
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  14. Gustavo C. Ferreira
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  15. Patrícia F. Schuck
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  16. Emilio L. Streck
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Corresponding author

Correspondence to Emilio L. Streck.

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All experimental procedures were carried out in accordance with the Guide for the Care and Use of Laboratory Animals issued by the National Institutes of Health and received an approval from the Ethics Committee of the Universidade do Extremo Sul Catarinense.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Gomes, L.M., Scaini, G., Carvalho-Silva, M. et al. Antioxidants Reverse the Changes in the Cholinergic System Caused by L-Tyrosine Administration in Rats. Neurotox Res 34, 769–780 (2018). https://doi.org/10.1007/s12640-018-9866-6

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  • DOI: https://doi.org/10.1007/s12640-018-9866-6

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