Tubacin prevents neuronal migration defects and epileptic activity caused by rat Srpx2 silencing in utero. - Archive ouverte HAL
Article Dans Une Revue Brain - A Journal of Neurology Année : 2013

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

Manal Salmi
  • Fonction : Auteur
Nadine Bruneau
  • Fonction : Auteur
Jennifer Cillario
  • Fonction : Auteur
Natalia Lozovaya
  • Fonction : Auteur
Annick Massacrier
  • Fonction : Auteur
Robin Cloarec
  • Fonction : Auteur
Timur Tsintsadze
  • Fonction : Auteur
Vera Tsintsadze
  • Fonction : Auteur
Lan Bao
  • Fonction : Auteur
Vanessa Pauly
  • Fonction : Auteur
Nail Burnashev
  • Fonction : Auteur
Pierre Szepetowski

Résumé

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.

Dates et versions

hal-00862156 , version 1 (16-09-2013)

Identifiants

Citer

Manal Salmi, Nadine Bruneau, Jennifer Cillario, Natalia Lozovaya, Annick Massacrier, et al.. Tubacin prevents neuronal migration defects and epileptic activity caused by rat Srpx2 silencing in utero.. Brain - A Journal of Neurology , 2013, 136 (Pt 8), pp.2457-73. ⟨10.1093/brain/awt161⟩. ⟨hal-00862156⟩
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