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

• DOI: 10.1093/brain/awt161
• Publication Date: 2013-07-06T03:23:45Z
• Authors: Manal Salmi; Nadine Bruneau; Jennifer Cillario; Natalia Lozovaya; Annick Massacrier; Emmanuelle Buhler; Robin Cloarec; Timur Tsintsadze; Françoise Watrin; Vera Tsintsadze; Céline Zimmer; Claude Villard; Daniel Lafitte; Carlos Cardoso; Lan Bao; Gaetan Lesca; Gabrielle Rudolf; Françoise Muscatelli; Vanessa Pauly; Ilgam Khalilov; Pascale Durbec; Yehezkel Ben-Ari; Nail Burnashev; Alfonso Represa; Pierre Szepetowski
• Keywords: 0301 basic medicine; [SDV]Life Sciences [q-bio]; [SDV.BC]Life Sciences [q-bio]/Cellular Biology; Hydroxamic Acids; 618; 03 medical and health sciences; Cell Movement; Tubulin; 616; Srpx2; in utero prevention; Animals; Humans; Anilides; Gene Silencing; [SDV.BC] Life Sciences [q-bio]/Cellular Biology; Cerebral Cortex; Neurons; neuronal migration; Epilepsy; Membrane Proteins; developmental epilepsy; Rats; 3. Good health; [SDV] Life Sciences [q-bio]; Histone Deacetylase Inhibitors; tubulin acetylation

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 therapeutic issues. Two missense mutations sushi repeat-containing protein SRPX2 had been previously identified disorders or without structural developmental alteration speech cortex. In present study, we aimed to decipher precise role SRPX2, have a better knowledge on consequences its mutations, start addressing issues through design an appropriate animal model. Using utero Srpx2 silencing approach, show that influences neuronal migration developing rat Wild-type, but not mutant proteins, rescued phenotype caused by utero, increased alpha-tubulin acetylation. Following silencing, spontaneous epileptiform activity was recorded post-natally. The defects post-natal were prevented early embryos maternal administration tubulin deacetylase inhibitor tubacin. Hence manifestations origin could be using transient drug-based protocol.