دورية أكاديمية
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Socrates: A Novel N-Ethyl-N-nitrosourea-Induced Mouse Mutant with Audiogenic Epilepsy.

التفاصيل البيبلوغرافية
العنوان: Socrates: A Novel N-Ethyl-N-nitrosourea-Induced Mouse Mutant with Audiogenic Epilepsy.
المؤلفون: Varlamova EG; Institute of Cell Biophysics of the Russian Academy of Sciences, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Russia., Borisova EV; Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.; Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia., Evstratova YA; Federal State Budgetary Educational Institution of Higher Education 'MIREA-Russian Technological University', 78, Vernadskogo Ave., 119454 Moscow, Russia., Newman AG; Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany., Kuldaeva VP; Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia.; Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 10 Nab. Ushaiki, 634050 Tomsk, Russia., Gavrish MS; Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia., Kondakova EV; Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia.; Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 10 Nab. Ushaiki, 634050 Tomsk, Russia., Tarabykin VS; Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.; Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia.; Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 10 Nab. Ushaiki, 634050 Tomsk, Russia., Babaev AA; Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia., Turovsky EA; Institute of Cell Biophysics of the Russian Academy of Sciences, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Russia.; Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2023 Dec 04; Vol. 24 (23). Date of Electronic Publication: 2023 Dec 04.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Epilepsy, Reflex*/genetics , Epilepsy, Reflex*/metabolism, Child ; Animals ; Humans ; Mice ; Ethylnitrosourea/toxicity ; Large-Conductance Calcium-Activated Potassium Channels/metabolism ; Anticonvulsants/pharmacology ; Brain/metabolism ; Disease Models, Animal
مستخلص: Epilepsy is one of the common neurological diseases that affects not only adults but also infants and children. Because epilepsy has been studied for a long time, there are several pharmacologically effective anticonvulsants, which, however, are not suitable as therapy for all patients. The genesis of epilepsy has been extensively investigated in terms of its occurrence after injury and as a concomitant disease with various brain diseases, such as tumors, ischemic events, etc. However, in the last decades, there are multiple reports that both genetic and epigenetic factors play an important role in epileptogenesis. Therefore, there is a need for further identification of genes and loci that can be associated with higher susceptibility to epileptic seizures. Use of mouse knockout models of epileptogenesis is very informative, but it has its limitations. One of them is due to the fact that complete deletion of a gene is not, in many cases, similar to human epilepsy-associated syndromes. Another approach to generating mouse models of epilepsy is N-Ethyl-N-nitrosourea (ENU)-directed mutagenesis. Recently, using this approach, we generated a novel mouse strain, soc ( socrates , formerly s8-3 ), with epileptiform activity. Using molecular biology methods, calcium neuroimaging, and immunocytochemistry, we were able to characterize the strain. Neurons isolated from soc mutant brains retain the ability to differentiate in vitro and form a network. However, soc mutant neurons are characterized by increased spontaneous excitation activity. They also demonstrate a high degree of Ca 2+ activity compared to WT neurons. Additionally, they show increased expression of NMDA receptors, decreased expression of the Ca 2+ -conducting GluA2 subunit of AMPA receptors, suppressed expression of phosphoinositol 3-kinase, and BK channels of the cytoplasmic membrane involved in protection against epileptogenesis. During embryonic and postnatal development, the expression of several genes encoding ion channels is downregulated in vivo, as well. Our data indicate that soc mutation causes a disruption of the excitation-inhibition balance in the brain, and it can serve as a mouse model of epilepsy.
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معلومات مُعتمدة: (project №FSWR-2023-0029). Ministry of science and higher education of the Russian Federation
فهرسة مساهمة: Keywords: calcium ions; epileptiform activity; gene expression; mutagenesis; neurons; receptors; signaling
المشرفين على المادة: P8M1T4190R (Ethylnitrosourea)
0 (Large-Conductance Calcium-Activated Potassium Channels)
0 (Anticonvulsants)
تواريخ الأحداث: Date Created: 20231209 Date Completed: 20231216 Latest Revision: 20231216
رمز التحديث: 20231217
مُعرف محوري في PubMed: PMC10707124
DOI: 10.3390/ijms242317104
PMID: 38069426
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms242317104