Karolina Niźinska, Maciej Olszewski, Dorota Nowicka, Kinga Szydłowska, Kinga Nazaruk, Katarzyna Łukasiuk
{"title":"甲基CpG结合结构域3在癫痫发作和癫痫发生中的作用。","authors":"Karolina Niźinska, Maciej Olszewski, Dorota Nowicka, Kinga Szydłowska, Kinga Nazaruk, Katarzyna Łukasiuk","doi":"10.55782/ane-2025-2706","DOIUrl":null,"url":null,"abstract":"<p><p>Methyl‑CpG binding domain protein 3 (Mbd3), a component of the NuRD chromatin remodeling complex, plays a role in transcriptional regulation and has been implicated in neuronal development; however, its role in epilepsy remains unclear. This study investigated the effects of Mbd3 downregulation on seizure susceptibility and behavior in rats, using adeno‑associated viral vectors that code for short hairpin RNA to downregulate Mbd3 expression in the basolateral amygdala. Behavioral assessments included the open field test, elevated plus maze test, and hyperexcitability test. Seizure susceptibility was evaluated using the PTZ challenge and PTZ kindling models. A decreased Mbd3 level significantly increased latency to seizure onset in the PTZ challenge, indicating a raised seizure threshold. Rats with reduced Mbd3 expression also exhibited increased anxiety‑like behavior in the open‑field test. Mbd3 downregulation did not affect the progression of epileptogenesis in the PTZ kindling model. These findings suggest that Mbd3 contributes to acute seizure susceptibility and emotional behavior but not to the long‑term development of epilepsy, highlighting its potential as an epigenetic modulator in seizure regulation.</p>","PeriodicalId":7032,"journal":{"name":"Acta neurobiologiae experimentalis","volume":"85 2","pages":"67-74"},"PeriodicalIF":1.4000,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The role of methyl‑CpG binding domain 3 in seizures and epileptogenesis.\",\"authors\":\"Karolina Niźinska, Maciej Olszewski, Dorota Nowicka, Kinga Szydłowska, Kinga Nazaruk, Katarzyna Łukasiuk\",\"doi\":\"10.55782/ane-2025-2706\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Methyl‑CpG binding domain protein 3 (Mbd3), a component of the NuRD chromatin remodeling complex, plays a role in transcriptional regulation and has been implicated in neuronal development; however, its role in epilepsy remains unclear. This study investigated the effects of Mbd3 downregulation on seizure susceptibility and behavior in rats, using adeno‑associated viral vectors that code for short hairpin RNA to downregulate Mbd3 expression in the basolateral amygdala. Behavioral assessments included the open field test, elevated plus maze test, and hyperexcitability test. Seizure susceptibility was evaluated using the PTZ challenge and PTZ kindling models. A decreased Mbd3 level significantly increased latency to seizure onset in the PTZ challenge, indicating a raised seizure threshold. Rats with reduced Mbd3 expression also exhibited increased anxiety‑like behavior in the open‑field test. Mbd3 downregulation did not affect the progression of epileptogenesis in the PTZ kindling model. These findings suggest that Mbd3 contributes to acute seizure susceptibility and emotional behavior but not to the long‑term development of epilepsy, highlighting its potential as an epigenetic modulator in seizure regulation.</p>\",\"PeriodicalId\":7032,\"journal\":{\"name\":\"Acta neurobiologiae experimentalis\",\"volume\":\"85 2\",\"pages\":\"67-74\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2025-07-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta neurobiologiae experimentalis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.55782/ane-2025-2706\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta neurobiologiae experimentalis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.55782/ane-2025-2706","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
The role of methyl‑CpG binding domain 3 in seizures and epileptogenesis.
Methyl‑CpG binding domain protein 3 (Mbd3), a component of the NuRD chromatin remodeling complex, plays a role in transcriptional regulation and has been implicated in neuronal development; however, its role in epilepsy remains unclear. This study investigated the effects of Mbd3 downregulation on seizure susceptibility and behavior in rats, using adeno‑associated viral vectors that code for short hairpin RNA to downregulate Mbd3 expression in the basolateral amygdala. Behavioral assessments included the open field test, elevated plus maze test, and hyperexcitability test. Seizure susceptibility was evaluated using the PTZ challenge and PTZ kindling models. A decreased Mbd3 level significantly increased latency to seizure onset in the PTZ challenge, indicating a raised seizure threshold. Rats with reduced Mbd3 expression also exhibited increased anxiety‑like behavior in the open‑field test. Mbd3 downregulation did not affect the progression of epileptogenesis in the PTZ kindling model. These findings suggest that Mbd3 contributes to acute seizure susceptibility and emotional behavior but not to the long‑term development of epilepsy, highlighting its potential as an epigenetic modulator in seizure regulation.
期刊介绍:
Acta Neurobiologiae Experimentalis (ISSN: 0065-1400 (print), eISSN: 1689-0035) covers all aspects of neuroscience, from molecular and cellular neurobiology of the nervous system, through cellular and systems electrophysiology, brain imaging, functional and comparative neuroanatomy, development and evolution of the nervous system, behavior and neuropsychology to brain aging and pathology, including neuroinformatics and modeling.