1. Spatiotemporal characterization of mTOR kinase activity following kainic acid induced status epilepticus and analysis of rat brain response to chronic rapamycin treatment
- Author
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Agnieszka Skalecka, Bartosz Caban, Magdalena Blazejczyk, Jacek Jaworski, Matylda Macias, Bartosz Tarkowski, Anna Rodo, P Kazmierska, and Jan Konopacki
- Subjects
Male ,lcsh:Medicine ,Pharmacology ,Hippocampus ,Phosphoserine ,0302 clinical medicine ,Status Epilepticus ,Molecular Cell Biology ,Neurobiology of Disease and Regeneration ,Phosphorylation ,lcsh:Science ,Neurons ,0303 health sciences ,Ribosomal Protein S6 ,Multidisciplinary ,Kainic Acid ,Protein Kinase Signaling Cascade ,Cell Death ,TOR Serine-Threonine Kinases ,Brain ,Animal Models ,Signaling Cascades ,Neurology ,Medicine ,medicine.symptom ,medicine.drug ,Research Article ,Signal Transduction ,Hydrocephalus ,Subcellular Fractions ,medicine.medical_specialty ,Programmed cell death ,Status epilepticus ,Biology ,Signaling Pathways ,03 medical and health sciences ,Model Organisms ,Spatio-Temporal Analysis ,Seizures ,Internal medicine ,Genetic model ,medicine ,Animals ,Kinase activity ,Rats, Wistar ,PI3K/AKT/mTOR pathway ,030304 developmental biology ,Cell Nucleus ,Sirolimus ,Epilepsy ,RPTOR ,lcsh:R ,Rats ,Endocrinology ,Astrocytes ,Rat ,lcsh:Q ,Molecular Neuroscience ,030217 neurology & neurosurgery ,Neuroscience - 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.
- Published
- 2013