title: Spatiotemporal characterization of mTOR kinase activity following kainic acid induced status epilepticus and analysis of rat brain response to chronic rapamycin treatment.
abstract: Mammalian target of rapamycin (mTOR) is a protein kinase that senses nutrient availability, trophic factors support, cellular energy level, cellular stress, and neurotransmitters and adjusts cellular metabolism accordingly. Adequate mTOR activity is needed for development as well as proper physiology of mature neurons. Consequently, changes in mTOR activity are often observed in neuropathology. Recently, several groups reported that seizures increase mammalian target of rapamycin (mTOR) kinase activity, and such increased activity in genetic models can contribute to spontaneous seizures. However, the current knowledge about the spatiotemporal pattern of mTOR activation induced by proconvulsive agents is rather rudimentary. Also consequences of insufficient mTOR activity on a status epilepticus are poorly understood. Here, we systematically investigated these two issues. We showed that mTOR signaling was activated by kainic acid (KA)-induced status epilepticus through several brain areas, including the hippocampus and cortex as well as revealed two waves of mTOR activation: an early wave (2 h) that occurs in neurons and a late wave that predominantly occurs in astrocytes. Unexpectedly, we found that pretreatment with rapamycin, a potent mTOR inhibitor, gradually (i) sensitized animals to KA treatment and (ii) induced gross anatomical changes in the brain.
authors.affiliation: Laboratory of Molecular and Cell Neurobiology, International Institute of Molecular and Cell Biology, Warsaw, Poland.
authors.forename: Matylda
authors.initials: M
authors.lastname: Macias
authors.forename: Magdalena
authors.initials: M
authors.lastname: Blazejczyk
authors.forename: Paulina
authors.initials: P
authors.lastname: Kazmierska
authors.forename: Bartosz
authors.initials: B
authors.lastname: Caban
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Skalecka
authors.forename: Bartosz
authors.initials: B
authors.lastname: Tarkowski
authors.forename: Anna
authors.initials: A
authors.lastname: Rodo
authors.forename: Jan
authors.initials: J
authors.lastname: Konopacki
authors.forename: Jacek
authors.initials: J
authors.lastname: Jaworski
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007608:Kainic Acid; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D038601:Ribosomal Protein S6 / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D062211:Spatio-Temporal Analysis; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D038601:Ribosomal Protein S6; D010768:Phosphoserine; D058570:TOR Serine-Threonine Kinases; D007608:Kainic Acid; D020123:Sirolimus