Functional state of the nigrostriatal system of Krushinsky – Molodkina rats during audiogenic seizure expression
Neurochemical mechanisms of initiation and expression of epileptic seizures are poorly explored, and there are no published data that could demonstrate the functional state of the neuromediator systems at the initial state of seizure in the animals genetically prone to seizure. In the current work, ...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2016-05-01
|
| Series: | Вавиловский журнал генетики и селекции |
| Subjects: | |
| Online Access: | https://vavilov.elpub.ru/jour/article/view/587 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832575216962764800 |
|---|---|
| author | N. A. Dorofeeva L. S. Nikitina D. V. Zosen M. V. Glazova E. V. Chernigovskaya |
| author_facet | N. A. Dorofeeva L. S. Nikitina D. V. Zosen M. V. Glazova E. V. Chernigovskaya |
| author_sort | N. A. Dorofeeva |
| collection | DOAJ |
| description | Neurochemical mechanisms of initiation and expression of epileptic seizures are poorly explored, and there are no published data that could demonstrate the functional state of the neuromediator systems at the initial state of seizure in the animals genetically prone to seizure. In the current work, we studied the role of extracellular signal-regulated kinase (ERK1/2) in the regulation of the nigrostriatal glutamate, GABA and dopamine neurons of Krushinsky – Molodkina rats at clonus-tonus and ataxia stages of audiogenic seizure. We demonstrated upregulation of ERK1/2 activity upon audio stimulation which was accompanied by increased activation of Synapsin I in the striatum and substantia nigra in comparison to intact Krushinsky – Molodkina rats. The observed exocytosis activation led to secretion of glutamate in the striatum and, as a result, to stimulation of seizures. However, at clonus-tonus stage in the striatum we revealed the changes that could participate in further inhibition of seizure activity, such as increased phosphorylation of tyrosine hydroxylase upon increased ERK1/2 activity followed by activation of dopamine release in the pars compacta of the substantia nigra. At the same time, enhanced D2 and increased D1 dopamine receptor contents were observed. These data revealed attenuation of direct (pro-seizure) and indirect (anti-seizure) pathways of the regulation of the substantia nigra GABA neurons. We demonstrated activation of GABA in the substantia nigra pars reticulate, which probably results in the inhibition of glutamate neurons of the thalamus and could be one of the mechanisms inhibiting seizure activity during ataxia. |
| format | Article |
| id | doaj-art-2e97f15991e146fbbe1f3a01cf256111 |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2016-05-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-2e97f15991e146fbbe1f3a01cf2561112025-02-01T09:58:02ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592016-05-0120220421110.18699/VJ16.146466Functional state of the nigrostriatal system of Krushinsky – Molodkina rats during audiogenic seizure expressionN. A. Dorofeeva0L. S. Nikitina1D. V. Zosen2M. V. Glazova3E. V. Chernigovskaya4Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint- Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint- Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint- Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint- Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint- Petersburg, RussiaNeurochemical mechanisms of initiation and expression of epileptic seizures are poorly explored, and there are no published data that could demonstrate the functional state of the neuromediator systems at the initial state of seizure in the animals genetically prone to seizure. In the current work, we studied the role of extracellular signal-regulated kinase (ERK1/2) in the regulation of the nigrostriatal glutamate, GABA and dopamine neurons of Krushinsky – Molodkina rats at clonus-tonus and ataxia stages of audiogenic seizure. We demonstrated upregulation of ERK1/2 activity upon audio stimulation which was accompanied by increased activation of Synapsin I in the striatum and substantia nigra in comparison to intact Krushinsky – Molodkina rats. The observed exocytosis activation led to secretion of glutamate in the striatum and, as a result, to stimulation of seizures. However, at clonus-tonus stage in the striatum we revealed the changes that could participate in further inhibition of seizure activity, such as increased phosphorylation of tyrosine hydroxylase upon increased ERK1/2 activity followed by activation of dopamine release in the pars compacta of the substantia nigra. At the same time, enhanced D2 and increased D1 dopamine receptor contents were observed. These data revealed attenuation of direct (pro-seizure) and indirect (anti-seizure) pathways of the regulation of the substantia nigra GABA neurons. We demonstrated activation of GABA in the substantia nigra pars reticulate, which probably results in the inhibition of glutamate neurons of the thalamus and could be one of the mechanisms inhibiting seizure activity during ataxia.https://vavilov.elpub.ru/jour/article/view/587krushinsky–molodkina ratsimmunohistochemistrywestern blotnigrostriatal bundledopamine neuronsd1 and d2 dopamine receptorserk1/2glutamategabasynapsin 1 |
| spellingShingle | N. A. Dorofeeva L. S. Nikitina D. V. Zosen M. V. Glazova E. V. Chernigovskaya Functional state of the nigrostriatal system of Krushinsky – Molodkina rats during audiogenic seizure expression Вавиловский журнал генетики и селекции krushinsky–molodkina rats immunohistochemistry western blot nigrostriatal bundle dopamine neurons d1 and d2 dopamine receptors erk1/2 glutamate gaba synapsin 1 |
| title | Functional state of the nigrostriatal system of Krushinsky – Molodkina rats during audiogenic seizure expression |
| title_full | Functional state of the nigrostriatal system of Krushinsky – Molodkina rats during audiogenic seizure expression |
| title_fullStr | Functional state of the nigrostriatal system of Krushinsky – Molodkina rats during audiogenic seizure expression |
| title_full_unstemmed | Functional state of the nigrostriatal system of Krushinsky – Molodkina rats during audiogenic seizure expression |
| title_short | Functional state of the nigrostriatal system of Krushinsky – Molodkina rats during audiogenic seizure expression |
| title_sort | functional state of the nigrostriatal system of krushinsky molodkina rats during audiogenic seizure expression |
| topic | krushinsky–molodkina rats immunohistochemistry western blot nigrostriatal bundle dopamine neurons d1 and d2 dopamine receptors erk1/2 glutamate gaba synapsin 1 |
| url | https://vavilov.elpub.ru/jour/article/view/587 |
| work_keys_str_mv | AT nadorofeeva functionalstateofthenigrostriatalsystemofkrushinskymolodkinaratsduringaudiogenicseizureexpression AT lsnikitina functionalstateofthenigrostriatalsystemofkrushinskymolodkinaratsduringaudiogenicseizureexpression AT dvzosen functionalstateofthenigrostriatalsystemofkrushinskymolodkinaratsduringaudiogenicseizureexpression AT mvglazova functionalstateofthenigrostriatalsystemofkrushinskymolodkinaratsduringaudiogenicseizureexpression AT evchernigovskaya functionalstateofthenigrostriatalsystemofkrushinskymolodkinaratsduringaudiogenicseizureexpression |