title: Mouse hippocampal phosphorylation footprint induced by generalized seizures: Focus on ERK, mTORC1 and Akt/GSK-3 pathways.
abstract: Exacerbated hippocampal activity has been associated to critical modifications of the intracellular signaling pathways. We have investigated rapid hippocampal adaptive responses induced by maximal electroshock seizure (MES). Here, we demonstrate that abnormal and exacerbated hippocampal activity induced by MES triggers specific and temporally distinct patterns of phosphorylation of extracellular signal-related kinase (ERK), mammalian target of rapamycin complex (mTORC) and Akt/glycogen synthase kinase-3 (Akt/GSK-3) pathways in the mouse hippocampus. While the ERK pathway is transiently activated, the mTORC1 cascade follows a rapid inhibition followed by a transient activation. This rebound of mTORC1 activity leads to the selective phosphorylation of p70S6K, which is accompanied by an enhanced phosphorylation of the ribosomal subunit S6. In contrast, the Akt/GSK-3 pathway is weakly altered. Finally, MES triggers a rapid upregulation of several plasticity-associated genes as a consequence exacerbated hippocampal activity. The results reported in the present study are reminiscent of the one observed in other models of generalized seizures, thus defining a common molecular footprint induced by intense and aberrant hippocampal activities.
authors.affiliation: CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier F-34094, France; Inserm U1191, Montpellier F-34094, France; Université de Montpellier, Montpellier F-34094, France. Electronic address: peppe.ganga@gmail.com.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gangarossa
authors.affiliation: CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier F-34094, France; Inserm U1191, Montpellier F-34094, France; Université de Montpellier, Montpellier F-34094, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Sakkaki
authors.affiliation: CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier F-34094, France; Inserm U1191, Montpellier F-34094, France; Université de Montpellier, Montpellier F-34094, France; LabEx 'Ion Channel Science and Therapeutics', Montpellier F-34094, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lory
authors.affiliation: CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier F-34094, France; Inserm U1191, Montpellier F-34094, France; Université de Montpellier, Montpellier F-34094, France. Electronic address: emmanuel.valjent@igf.cnrs.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Valjent
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004569:Electroencephalography; D004597:Electroshock; D004829:Epilepsy, Generalized / Q000201:enzymology* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology; D000076222:Mechanistic Target of Rapamycin Complex 1; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011897:Random Allocation; D012640:Seizures / Q000201:enzymology* / Q000473:pathology; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D038362:Glycogen Synthase Kinase 3
keywords: Akt/GSK-3; ERK1/2; immediate early genes; mTORC; seizures; signal transduction