title: The mTOR signaling pathway and neuronal stem/progenitor cell proliferation in the hippocampus are altered during the development of absence epilepsy in a genetic animal model.
abstract: Hyperactivation of mammalian target of rapamycin (mTOR) signaling pathway occurs after an epileptogenic insult and, its inhibition prevents the development of spontaneous seizures. We have recently demonstrated that mTOR's inhibition by rapamycin (started before seizure onset), permanently reduces the development of spontaneous absence seizures in WAG/Rij rats, an animal model of absence epilepsy; furthermore, mTOR phosphorylation was increased in adult WAG/Rij rats' cortex, but not other brain areas. However, it was not clear whether this hyperphosphorylation was a cause or a consequence of absence seizure. Here, we have addressed this issue by analyzing immunohistochemically: (1) the brain levels of total and phosphorylated mTOR in young (before seizures) and adult WAG/Rij rats; (2) the proliferation of hippocampal neuronal stem/progenitor cells assessed by BrdU analysis at different ages. WAG/Rij rats have higher levels of total mTOR in several brain areas than Wistar rats; phospho-mTOR staining is higher in young WAG/Rij rats than control and adult WAG/Rij rats. Finally, the age-related decline in hippocampal neural progenitor cell proliferation rate was slower in WAG/Rij than Wistar rats. Our results support a role for persistent mTOR activation and consequent change in hippocampal progenitor cell proliferation during the epileptogenic process leading to the development of absence seizures in WAG/Rij rats.
authors.affiliation: Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, Viale Europa, Germaneto, 88100, Catanzaro, Italy, erusso@unicz.it.
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
authors.forename: Paolo
authors.initials: P
authors.lastname: Follesa
authors.forename: Rita
authors.initials: R
authors.lastname: Citraro
authors.forename: Caterina
authors.initials: C
authors.lastname: Camastra
authors.forename: Annalidia
authors.initials: A
authors.lastname: Donato
authors.forename: Daniela
authors.initials: D
authors.lastname: Isola
authors.forename: Andrew
authors.initials: A
authors.lastname: Constanti
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Donato
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D004195:Disease Models, Animal; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D058953:Neural Stem Cells / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases