Homocysteine, Neurotoxicity and Hyperexcitability
| Autor: | Veselinka Šušić, Olivera Stanojlović, Dragan Djuric, Aleksandra Rašić-Marković, Dragan Hrnčić |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
0303 health sciences
Homocysteine Chemistry Metabolite Central nervous system Neurotoxicity Excitotoxicity Transsulfuration pathway Pharmacology medicine.disease medicine.disease_cause 3. Good health 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine.anatomical_structure Convulsant Systemic administration medicine 030217 neurology & neurosurgery 030304 developmental biology |
| Zdroj: | NATO Science for Peace and Security Series A: Chemistry and Biology ISBN: 9789400765122 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|