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Advanced Bioactive Compounds Countering the Effects of Radiological, Chemical and Biological Agents pp 73–81Cite as

Homocysteine, Neurotoxicity and Hyperexcitability

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Abstract

The research efforts worldwide have established the sulphur-containing amino acid homocysteine (Hcy) as a potent and independent risk factor (or risk marker) for a number of cardiovascular, as well as central nervous system disorders. This vasotoxic and neurotoxic agent interferes with fundamental biological ­processes and it is metabolized to homocysteine thiolactone, its highly reactive thioester. Hcy and its metabolites induced neuronal damage and cell loss through excitotoxicity and apoptosis. Our results showed that Hcy and Hcy thiolactone ­significantly affect neuronal cycles, EEG tracings and behavioral responses. After systemic administration, this naturally occurred substance led to the appearance of two different kinds of epileptic activity in adult rats. It has been suggested that Hcy thiolactone may be considered as an excitatory metabolite, capable of becoming a convulsant if accumulated to a greater extent in the brain. It was also found that changes in Na+/K+-ATPase activity could be an important factor for the ­establishment of epileptic focus in Hcy-treated rats. Recently, we demonstrated functional ­involvement of NO signaling pathway in mechanisms of hyperexcitability caused by Hcy thiolactone. Acute ethanol treatment was shown in our study to decrease EEG power spectra and to represent one of the factors of the exogenous stabilization of brain excitability. Furthermore, our preliminary results showed that hypermethionine diet could contribute to these effects. Developed model of Hcy thiolactone-­induced seizures in adult rats allows further investigations of mechanisms involved in Hcy's neurotoxicity and hyperexcitability.

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Acknowledgments 

This work was supported by the Ministry of Education and Science, Grant No. 175032

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Authors and Affiliations

  1. Institute of Medical Physiology “Richard Burian”, School of Medicine, University of Belgrade, Visegradska St., 26/II, 11000, Belgrade, Serbia

    Olivera Stanojlović, Dragan Hrnčić, Aleksandra Rašić-Marković & Dragan Djuric

  2. Institute of Medical Physiology “Richard Burian”, School of Medicine, University of Belgrade, 35 Knez Mihailova St., 11001, Belgrade, Serbia

    Veselinka Šušić

Authors
  1. Olivera Stanojlović
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  2. Dragan Hrnčić
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  3. Aleksandra Rašić-Marković
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  4. Veselinka Šušić
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  5. Dragan Djuric
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Corresponding author

Correspondence to Olivera Stanojlović .

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Editors and Affiliations

  1. St. Boniface Hospital Research Centre, Tache Ave 351, Winnipeg, R2H 2A6, Canada

    Grant N. Pierce

  2. , Division of Health and Rehabilitation, Crimean State Humanitarian University, Sevastopolskaya St. 2, Yalta, Crimea, 98635, Ukraine

    Volodymyr I. Mizin

  3. St. Boniface Hospital Research Centre, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Alexander Omelchenko

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Stanojlović, O., Hrnčić, D., Rašić-Marković, A., Šušić, V., Djuric, D. (2013). Homocysteine, Neurotoxicity and Hyperexcitability. In: Pierce, G., Mizin, V., Omelchenko, A. (eds) Advanced Bioactive Compounds Countering the Effects of Radiological, Chemical and Biological Agents. NATO Science for Peace and Security Series A: Chemistry and Biology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6513-9_6

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