Mutation in the Sip1 transcription factor leads to a disturbance of the preconditioning of AMPA receptors by episodes of hypoxia in neurons of the cerebral cortex due to changes in their activity and subunit composition. The protective effects of interleukin-10
| Autor: | Valery P. Zinchenko, Victor Tarabykin, Egor A. Turovsky, A.A. Babaev, Ekaterina A. Epifanova, Maria V. Turovskaya |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Agonist medicine.drug_class Biophysics Nerve Tissue Proteins AMPA receptor Biochemistry 03 medical and health sciences Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine Neuroplasticity medicine Excitatory Amino Acid Agonists Animals Calcium Signaling Receptors AMPA Hypoxia Molecular Biology Cerebral Cortex Neurons Alanine Chemistry Hypoxia (medical) Cell biology Interleukin-10 Enzyme Activation Interleukin 10 030104 developmental biology medicine.anatomical_structure Pyrimidines nervous system Microscopy Fluorescence Cerebral cortex Mutation Excitatory postsynaptic potential Calcium Brainstem medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Archives of biochemistry and biophysics. 654 |
| ISSN: | 1096-0384 |
| Popis: | The Sip1 mutation plays the main role in pathogenesis of the Mowat-Wilson syndrome, which is characterized by the pronounced epileptic symptoms. Cortical neurons of homozygous mice with Sip1 mutation are resistant to AMPA receptor activators. Disturbances of the excitatory signaling components are also observed on such a phenomenon of neuroplasticity as hypoxic preconditioning. In this work, the mechanisms of loss of the AMPA receptor's ability to precondition by episodes of short-term hypoxia were investigated on cortical neurons derived from the Sip1 homozygous mice. The preconditioning effect was estimated by the level of suppression of the AMPA receptors activity with hypoxia episodes. Using fluorescence microscopy, we have shown that cortical neurons from the Sip1fl/fl mice are characterized by the absence of hypoxic preconditioning effect, whereas the amplitude of Ca2+-responses to the application of the AMPA receptor agonist, 5-Fluorowillardiine, in neurons from the Sip1 mice brainstem is suppressed by brief episodes of hypoxia. The mechanism responsible for this process is hypoxia-induced desensitization of the AMPA receptors, which is absent in the cortex neurons possessing the Sip1 mutation. However, the appearance of preconditioning in these neurons can be induced by phosphoinositide-3-kinase activation with a selective activator or an anti-inflammatory cytokine interleukin-10. |
| Databáze: | OpenAIRE |
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