{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T21:45:59Z","timestamp":1767995159581,"version":"3.49.0"},"reference-count":46,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-24-00712"],"award-info":[{"award-number":["22-24-00712"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Genetic disorders affecting the functioning of the brain lead not only to the development of numerous hereditary diseases but also to the development of neurodegenerative and cognitive disorders. The result of this may be the disability of part of the able-bodied population. Almost all pathological states of the brain are characterized by serious defects in the intracellular and intercellular signaling of neurons and glial cells. At the same time, the mechanisms of disruption of these signaling cascades are not well understood due to the large number of molecules, including transcription factors that, when mutated, cause brain malformations. The transcription factor Satb1 is one of the least studied factors in the cerebral cortex, and the effects of its deletion in the postnatal brain are practically not studied. Hyperexcitability of neurons is observed in many genetic diseases of the nervous system (Hirschsprung\u2019s disease, Martin\u2013Bell syndrome, Huntington\u2019s disease, Alzheimer\u2019s, etc.), as well as in ischemic brain phenomena and convulsive and epileptic conditions of the brain. In turn, all these disorders of brain physiology are associated with defects in intracellular and intercellular signaling and are often the result of genetic disorders. Using Satb1 mutant mice and calcium neuroimaging, we show that Satb1 deletion in projection neurons of the neocortex causes downregulation of protein kinases PKC, CaMKII, and AKT\/PKB, while a partial deletion does not cause a dramatic disruption of kinome and Ca2+ signaling. As a result, Satb1-null neurons are characterized by increased spontaneous Ca2+ activity and hyperexcitability when modeling epileptiform activity. As a result of the deletion of Satb1, preconditioning mechanisms are disrupted in neurons during episodes of hypoxia. This occurs against the background of increased sensitivity of neurons to a decrease in the partial pressure of oxygen, which may indicate the vulnerability of neuronal networks and be accompanied by impaired expression of the Satb1 transcription factor. Here, we show that Satb1 deletion impaired the expression of a number of key kinases and neuronal hyperexcitation in models of epileptiform activity and hypoxia.<\/jats:p>","DOI":"10.3390\/biology12091207","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T10:14:11Z","timestamp":1693822451000},"page":"1207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Deletion of the Neuronal Transcription Factor Satb1 Induced Disturbance of the Kinome and Mechanisms of Hypoxic Preconditioning"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2528-8798","authenticated-orcid":false,"given":"Egor A.","family":"Turovsky","sequence":"first","affiliation":[{"name":"Institute of Cell Biophysics of the Russian Academy of Sciences, Federal Research Center \u201cPushchino Scientific Center for Biological Research of the Russian Academy of Sciences\u201d, 142290 Pushchino, Russia"},{"name":"Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viktor S.","family":"Tarabykin","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"},{"name":"Institute of Cell Biology and Neurobiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1158-5174","authenticated-orcid":false,"given":"Elena G.","family":"Varlamova","sequence":"additional","affiliation":[{"name":"Institute of Cell Biophysics of the Russian Academy of Sciences, Federal Research Center \u201cPushchino Scientific Center for Biological Research of the Russian Academy of Sciences\u201d, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nature04103","article-title":"Molecular insights into human brain evolution","volume":"437","author":"Hill","year":"2005","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/S1474-4422(14)70040-7","article-title":"Malformations of cortical development: Clinical features and genetic causes","volume":"13","author":"Guerrini","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.tins.2014.11.003","article-title":"Cerebral cortex assembly: Generating and reprogramming projection neuron diversity","volume":"38","author":"Lodato","year":"2015","journal-title":"Trends Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/j.celrep.2012.10.003","article-title":"Maturation-promoting activity of SATB1 in MGE-derived cortical interneurons","volume":"2","author":"Denaxa","year":"2012","journal-title":"Cell Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10935","DOI":"10.1523\/JNEUROSCI.1629-07.2007","article-title":"Spatial genetic patterning of the embryonic neuroepithelium generates GABAergic interneuron diversity in the adult cortex","volume":"27","author":"Fogarty","year":"2007","journal-title":"J. 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