Tubacin prevents neuronal migration defects and epileptic activity caused by rat Srpx2 silencing in utero

	Tubacin prevents neuronal migration defects and epileptic activity caused by rat Srpx2 silencing in utero
	Salmi, M; Bruneau, N; Cillario, J; Lozovaya, N; Massacrier, A; Buhler, E; Cloarec, R; Tsintsadze, T; Watrin, F; Tsintsadze, V
刊名	BRAIN
	2013
卷号	136 期号:1 页码:2457-2473
关键词	developmental epilepsy Srpx2 neuronal migration tubulin acetylation in utero prevention
通讯作者	Szepetowski, P (reprint author), INSERM, U901, Inst Neurobiol Mediterranee INMED, Parc Sci Luminy,BP13, F-13273 Marseille 09, France.,pierre.szepetowski@inserm.fr
英文摘要	Altered development of the human cerebral cortex can cause severe malformations with often intractable focal epileptic seizures and may participate in common pathologies, notably epilepsy. This raises important conceptual and therapeutic issues. Two missense mutations in the sushi repeat-containing protein SRPX2 had been previously identified in epileptic disorders with or without structural developmental alteration of the speech cortex. In the present study, we aimed to decipher the precise developmental role of SRPX2, to have a better knowledge on the consequences of its mutations, and to start addressing therapeutic issues through the design of an appropriate animal model. Using an in utero Srpx2 silencing approach, we show that SRPX2 influences neuronal migration in the developing rat cerebral cortex. Wild-type, but not the mutant human SRPX2 proteins, rescued the neuronal migration phenotype caused by Srpx2 silencing in utero, and increased alpha-tubulin acetylation. Following in utero Srpx2 silencing, spontaneous epileptiform activity was recorded post-natally. The neuronal migration defects and the post-natal epileptic consequences were prevented early in embryos by maternal administration of tubulin deacetylase inhibitor tubacin. Hence epileptiform manifestations of developmental origin could be prevented in utero, using a transient and drug-based therapeutic protocol.
学科主题	Neurosciences & Neurology
类目[WOS]	Clinical Neurology ; Neurosciences
关键词[WOS]	HISTONE DEACETYLASE INHIBITORS ; CENTRAL-NERVOUS-SYSTEM ; CORTICAL DEVELOPMENT ; CENTROTEMPORAL SPIKES ; ROLANDIC EPILEPSY ; RNA INTERFERENCE ; RADIAL MIGRATION ; CEREBRAL-CORTEX ; CELL-MIGRATION ; FETAL-BRAIN
收录类别	SCI
语种	英语
WOS记录号	WOS:000322338000018
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/512]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Salmi, M,Bruneau, N,Cillario, J,et al. Tubacin prevents neuronal migration defects and epileptic activity caused by rat Srpx2 silencing in utero[J]. BRAIN,2013,136(1):2457-2473.
APA	Salmi, M.,Bruneau, N.,Cillario, J.,Lozovaya, N.,Massacrier, A.,...&Szepetowski, P.(2013).Tubacin prevents neuronal migration defects and epileptic activity caused by rat Srpx2 silencing in utero.BRAIN,136(1),2457-2473.
MLA	Salmi, M,et al."Tubacin prevents neuronal migration defects and epileptic activity caused by rat Srpx2 silencing in utero".BRAIN 136.1(2013):2457-2473.